Document pe40X0R0zd0y913pM8Lzb0KVa

Dr. William Irwin DABT. ERT Ex. 6 Email: Tel: ex7 Toxicologist--Bioclseiiiist/Moleailar Biologist-ChemisU-Physieal Scientist EXPERIENCE SUMMARY: --Diplomat of the American Board of Toxicology (PAST Certification) --European Registered Toxicologist (ERT Board Certification) --Currently a GS-14 toxicologist as US EPA Structure Activity Team committee co-chair (detail) --Chair of US EPA Hazard and Risk Assessment Tech Team committee --Expert in analog identification, read across and structure-activity relationships (SAR) --Member of the OPP SAR read across team for 6 years (Residues Of Concern Knowledge team) --Regularly advise senior OPPT managers in read across and toxicology topics --Developed tools for read across endeavours (dermal & GI absorption, surfactancy calculators) --Developed and lead the Qualitative Risk Assessment Strategies team --Given briefings to division directors, office director and the Assistant Administrator --Given multiple presentations at public meetings representing the Agency (SOT, ACS) --Written several Technical Directives for contracting work projects --Worked on the team that developed 4 new Chemical Categories (Lung Effects Project) --High Quality Work: Published in Nature. PNAS. JBC. Arch. Tox., Book Chapters --My Independent Initiatives Vital to Project Successes --Very Motivated and Very Innovative --Very Independent, but Also a Team Plaver --Work at the Leading Edge of Fields --PhD in Biochemistrv/Molecular Biology --Experience at US EPA. Pfizer. Cerep, Lipton, GSK, ---BlflidLSniQr_SiiiiisLamYaliit_tiLa_GS14 --Hazard Characterization. Exposure Models & Risk Assessment for Chemicals --4.5 Years Postdoctoral Research in BioPhysics lab: Muscular Dystrophy, Mitochondrial Disease --BS in Chemistry. Physics. Mathematics --In vitro Assay Consultant --U.S. Patent (1st Author) --Process and Product Design --Mitochondrial Research Expert --Research in Italy, England. Croatia, USA --Muscle Research Expert --Primary and Tumor Cell Assay Experience --Research Has Led to Clinical Trials --Biotech Sales & Marketing --Research in Pharmaceutical. Toxicology, Food, Photographic, Protein Folding Areas --Research in Biotech. Purification and Environmental Areas --High Content Screening (HCS1 Microscopy Assay Expert --HTS Assay Design Expert (Biological. Chemical, Physical) --Teaching Experience in Biochemistry. Toxicology. Chemistry & Physics --In vivo Tumor Models and Animal Surgery --Toxicology Presentation with Professor Don Fox (C&D Toxicology Author) --4 Book Chanters (In vitro toxicology, endocrine-repro & development, protein folding) --Toxicology Journal Editor & Scientific Integrity Experience --QSAR and Risk Assessment Review Committee --US EPA Innovation Award (Lung Toxicity Project toxicology lead) -- Policy Contributions, Risk Assessment Forum, OECD LENA Sensitization Committee Position Qualifications and Education: I have sufficient college credits to qualify for Chemist, Biochemist, Physical Scientist, Biologist and Toxicologist. I am currently a co-chair of the read across Structure Activity Team, the perfect combination of skills for this SAR position. No other candidate may have degrees in all of the listed Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00001 categories (biology, toxicology, physical science, chemistry). I was on the OPP QSAR read across team (ROCKS) for 6 years and studied SAR for years in the pharmaceutical industry, thus I may be the most experience candidate for this SAR position. I have developed tools for read across in RAD, such as the dermal absorption project guidance, dermal absorption calculator and the surfactancy/solubility calculator. I developed and led the Qualitative Risk Assessment Strategies team and presented this project at the 2017 ACS meeting. I was the toxicology lead for Lung Effects Project, which developed four new Chemical Categories in OPPT and received an Innovation Award. I have written several Technical Directives for contracting work. I have given presentations on read across topics. I have briefed and advised senior management at the Director, Office Director and Assistant Administrator levels in the Agency. I worked for 4 years in the pharmaceutical industry with Pharmacology experience. I performed research on a muscular dystrophy therapy that later had successful clinical trials, so my combination of skills have been validated in the health sciences in practical terms. Senior Scientist; I was a senior scientist toxicologist in industry with people reporting to me, equivalent to a GS-14 senior scientist. I have certified for multiple GS14 positions previously (i.e. certification scores up to 98). I am currently a GS-14 senior scientist as the SAT SAR co-chair in RAD in OPPT (detail). Toxicology: >78 credit hours in biochemical toxicology research during PhD, 13 years professional experience as a toxicologist (Pfizer, GSK, Cellumen, US EPA), DABT board certification in toxicology, Book chapter on endocrine/developmental/reproductive toxicity of organotins, In Vitro and mitochondrial toxicology expert, Toxicology journal editor, seminars, etc. Applications of thermodynamics to toxicology SOT presentation with Dr. Don Fox (C&D Toxicology author). In vivo project on tumorigenesis of pesticide acetylaminofluorene (PNAS paper). I participated in a Scientific Advisory Panel on the pyrethroids. Toxicology assays patent. I gave 7 presentations to represent the US EPA at SOT meetings. Drug cumulative work in pharma. OECD LENA sensitization validation committee, US EPA Risk Assessment Forum, designed 10 ToxCAST assays, Co-chair of the US EPA Hazard and Risk Assessment Tech Team, Innovation Award for the US EPA Lung Toxicity Project as the toxicology lead, US EPA Focus committee member, US EPA Structure Activity committee Toxicology Experience: Endocrine disruption, Immunotoxicity, Cancer models, Myotoxicity, Blood Cell Toxicity, In vitro models, Hepatoxicity, Pharma models, Mitochondrial toxicity, Imaging toxicology, Dermal sensitization, Lung toxicology Biochemistrv-Biology-Health Sciences: PhD in biochemistry/molecular biology from the Sanford School of Medicine. Biochemistry is critical to Mechanism Of Action investigations. Animal surgery and physiology experience. My muscular dystrophy research was published in the prestigious journal Nature. The research led to a therapy with successful clinical trials which validated my health sciences qualifications. Chemistry; BS degree in analytical chemistry, >40 credit hours, worked as a research chemist for ~9 years with duties such as product/process development, chemical testing, assay development and water treatment/testing roles. I developed products for the pharmaceutical, medical and food technology industries. I developed P-Chem models for dermal exposure of chemicals and environmental fate. Physical Science: 35 credit hours in physics-engineering-electronics (24 credits needed for a major), taught electronics laboratory, performed physical testing methods in industry (viscosity, polarimetry hysteresis, solubility, Soxlet fat content, moisture content, etc). Physical-chemistry analysis for Quantitative Structural Activity Relationship modeling. Mathematics-Comnuter Science: 29 credit hours, Integral and differential calculus, Statistical Design of Experiments training, graphical data analysis skills, computer programming and design of computer circuits. Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00002 Pharmacology: I worked in the pharmaceutical industry for ~4 years, thus I learned the pharmacology of many drugs and pesticides (equivalent experience to a degree) based on experiments both in vivo and in vitro. I tested hundreds of drugs and chemicals for ontarget effects and adverse effects with in vitro toxicity assays. Volunteer Work: SOT educational outreach program volunteer, Chemistry tutor, agricultural extension agent volunteer, volunteer farm worker for low income people, chemistry lab instructor, electronics lab instructor, biochemistry lab instructor, ROCKS committee, RARC committee, Scientific Integrity Committee, HED Tox Study Group presenter, RAD template committee, CAPHRA Pyrethroid Committee and Scientific Advisory Panel Committee, Overseas muscle disease project for 4 years (lead to a successful human clinical trial), COOP volunteer (EPA continuity of operations project) R isk A ssessm ent Factor Leadership Policy Contributions Teamwork W illiam Irw in, PhD , D A B T , ER T Q ualifications Co-Chair of the US EPA Hazard and Risk Assessment Committee, Currently a GS-14 co-chair of the US EPA Structure Activity Team committee (detail); Supervised & Mentored many associates at Lipton, US EPA (HED, RAD), Pfizer, GSK, Cellumen (Chem., Tox., Biochem.); Briefed Lipton General Manager, Assistant Administrator, Deputy Assistant Administrator, Office Director and R&D Director on projects; Toxicology lead for the Lung Toxicity Project (Innovation Award); First Author Nature Paper (12 authors team, only 3 years), Risk Assessor, Acting Branch Chief, Mentored & Taught Environmental Chemistry & Biochemistry & Physics Laboratory, Independent: Initiated Pivotal Projects with little Supervision, Developed P-Chem model for exposure; Senior Scientist Toxicologist in Biotech equivalent to a GS14 (>2 years): Designed main company product, Patents 1st Author, supervised staff; Designed 10 ToxCAST Assays; Participated in a Scientific Advisory Panel on the pyrethroids; Designed Tox Imaging Assays (12 authors team paper, widely used assays, only 3 years), Overseas Muscular Dystrophy Therapy Team-- Successful Clinical Trials, 1st author on Nature paper, First Pyrethroid Hazard Model to Tox SAC, Industry Meetings, Tox Study Group Instruction, First Protocol to ToxSAC, Seminar on Mitochondrial Toxicity, Two Seminars on In Vitro Toxicology, Represented EPA in 7 SOT and one ACS Presentations, Book chapter on pesticide endocrine disruption, Maturity, Risk Assessment Forum, OECD Dermal Sensitization Assay Validation Team, Qualitative risk assessment team leader Pyrethroid Scientific Advisory Panel Committee Inhalation Policy Contributions Dermal Policy Contributions Gastro-Intestinal Policy Contributions Quantitative Structural Analysis Relationship Contributions Structural Alerts Policy Contributions Immunotoxicity Policy Contributions In Vitro Policy Contributions US EPA ToxCAST Assay Contributions Qualitative Risk Assessment Strategies HazRATT and SAT Committees co-chair; ROCKS QSAR Committee, RARC risk assessment committee, ToxSAC every meeting, CAPHRA team, Pyrethroids/Inhalation, Tox21, COOP, Inerts, Defibrillator team, EOGRTS reproduction study, Assisted other branches, Mitochondrial Tox resource, Scientific Integrity Committee, Risk Assessment Forum, OECD LLNA Validation Team, Document review and QC Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00003 Iiiferclisclplinary Analytical Research Toxicology Chemistry Physical Science Pharmacology Exposn re Mod eiing Biochemistry/Molecular Riology-MOA Knowledge Physiology Mathematics, Bata Analysis & Modeling Cancer Research Writing & Presentation Skills In Vitro & Tox21 Skills Training Honors Designed Physical & Chemical Analytical Assays as a research chemist (Process & Production Plant Experiments $20,000/day at times), Muscular Dystrophy Research (Biochemistry, Toxicology, Pharmacology & Physiology), Tox Assay Validation, ISO "9000" QC/QA, Imaging Tox Assays (biochemistry', optics, toxicology) Toxicologist, DABT Board Certification (peer status). Pharma, Biotech. Regulatory' Tox Experience >78 Tox Research credits during PhD, Clinical Chemistry, Tested Pesticides in Pharma, In Vitro Tox (Pesticide & Invertebrate Tox Models: rotenone, antimycin & cyanide), Bradford-Hill Analysis Chemistry Degree (44 Credits), ROCKS Member, Taught Environmental Chemistry Lab Research Chemist for ~9 years. Know DEEM Software, Water Treatment Expertise, QSAR Physics Degree (35 Credits, with electronics research & engineering). Taught Physics Laboratory Pharma Experience at Pfizer & GSK pharmaceuticals, Tox And A dd. Pharm. Journal Editing Developed P-Chem model to explain pesticide transfer from collars to fur to hand to mouth based on physics, biochemistry & chemistry partitioning & experience as a research chemist (RD Award). Lived on Farm 22 years: Used many herbicides, insecticides, fungicides. Physics & Chemistry degree gives understanding of important exposure factors (vapor pressure, mp, bp, viscosity, surface tension, partition coefficients, pKa, solubility, diffusion, charge, etc) PhD in Biochemistrv/Molecular Biology, MOA at molecular level skills. Taught Biochem Lab, Regularly review pesticide biochemistry papers for senior staff Muscular Dystrophy Research, Surgery in animals Mathematics Minor, Statistical Design of Experiments Course, "BMD" Calculations in pharma Cancer Postdoc research on herbicide Acetvlaminofluorene in vivo published in PNAS, Cancer presentation at SOT Nature paper (first author), papers in PNAS, JBC, Arch. Tox, Repro. & Dev. Toxicology Chapter, Two in vitro toxicology book chapters, protein folding book chapter. Papers cited over 1000 times. Journal Editing (JBC, TAAP, etc). Risk Assessments, Over 52 Seminars in 4 Countries (USA; London, Sandwich England; Zagreb, Vodice Designed & Adapted Assays >10 vears. Patents, In Vitro toxicology review articles. Assays implemented into ToxCAST I have helped train and mentor the newer toxicologists at Cellumen, Pfizer, GSK, US EPA (HED, RAD). I have supervised multiple research associates over the years, such as when I was a senior scientist in industry. I also participated in the student mentoring programs at the SOT meetings. My Nature paper has been cited over 359 times and led to other disease investigations. My imaging toxicology paper has been cited over 423 times and widely implemented and copied. DABT Toxicology Certification, European Registered Toxicologist (ERT board certification); Physics Honor Society , Mathematics Honor Society; US EPA Innovation Award; US EPA Bronze Medal Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00004 Experience: My mitochondrial research published in Nature led to successful clinical trials for a muscular dystrophy therapy. I have a very powerful skills set to be a versatile scientist with my toxicology background, research chemist work, and physics/mathematics degrees plus my direct experience with chemical exposure on a farm. Very few people possess my mix of skill. I have demonstrated teamwork, high productivity, quality assurance and customer service at several jobs, as demonstrated by my past bonus awards. I have skills in data analysis, developing new methods, teamwork and instruction on technical matters. I also have experience in hazard characterization, exposure and risk assessment of chemicals, plus quality control methods. In my past experience, I have planned and performed scientific investigations, developed new methods or adapted existing methods and validated these models, then implemented them in practical applications. I have originated projects and led them in my previous experience. I have developed interdisciplinary analytical procedures in toxicology, physics and chemistry areas. I have performed environmental sampling and testing to determine the exposure to waste products of industry. I have excellent analysis and problem solving skills, from the most advanced toxicology models in pharma. Obviously, I have pharmacology experience from working at Pfizer and GSK pharmaceuticals in the Safety Sciences Department (Toxicology/Pharmacology). At Pfizer, my main focus was developing advanced in vitro toxicology assays similar to the Tox21 initiative. At GSK my focus was antimicrobial compound research. I have presented many toxicology seminars in scientific meetings to various stakeholders in industry and the public, thus I appreciate the needs of various viewpoints. I have published my research in outstanding journals such as Nature Genetics, thus I have excellent communication skills. At Lipton, I was deeply involved in the ISO quality assurance (QA) implementation. A versatile scientist absolutely needs degrees in the multiple disciplines to perform at the higher levels, which is an interdisciplinary endeavor, with a PhD degree preferred. My background in toxicology from pharma provides excellent experience in the most advanced toxicology models in the world, an exceptional education for hazard characterization and risk assessment of chemicals/pesticides. My DABT board certification confirms that I am at the top of my field in toxicology, as evaluated by my peer toxicologists. I have a BS degree in Chemistry and functioned at a high level as a research chemist for about 9 years for Lipton. Thus, I well comprehend the chemistry aspects of hazard identification, also supported by my work on the US EPA ROCKS QSAR and Risk Assessment committees. I lived on a farm for 22 years, so I well understand the exposure aspect (ORE) of occupational chemical use, having directly applied pesticides many times myself. I also have a degree in Physics, and interpreting the physical properties of chemicals is crucial to interpreting their exposure potential (solubility, viscosity, melting point, hydrophobicity, surface tension, etc) and I have performed many of these physical tests myself. My environmental testing and water purification experience also aids my understanding of exposure to hazardous materials from industry. I have a PhD in Biochemistry/Molecular Biology which is very valuable in determining the mechanism of toxicity of chemicals (i.e. MOA), often the result of enzymatic inhibition or receptor binding or damage at the molecular level. Biochemistry is a strong bridging discipline between toxicology and residue chemistry. My mathematics minor is very valuable in complex calculations, advanced modeling, and statistical analysis. My supervisor at Lipton was a statistical modeler and I was taught statistical design of experiments techniques. I have considerable experience in computer programming which can aid modeling projects. I have >10 years experience developing in vitro toxicology assays and analysis. My experience with toxicology from pharma is very valuable, since some chemicals are also drugs or have the same mechanism of toxicity. Some pharma companies also make chemicals, so understanding their methods is important. I am continually seeking knowledge and science information, as demonstrated by my continued meeting attendance, presentations and publications. My memberships in the Physics Honor Society, Society of Toxicology, Diplomat of the American Board of Toxicology and Mathematics Honor Society demonstrate my consistent quest for excellence. I have taught in Chemistry, Biochemistry, Physics and Toxicology settings. Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00005 I | Introduction I I have over 10 years experience with product and assay development, with over j i 10 years experience in the pharmaceutical-related industry. I have worked for the US EPA. Pfizer, Cerep, j j Lipton, and GSK in product and assay development (risk & toxicology/pharmacology departments). I j ) have a BS in Analytical Chemistry, with other degrees in Physics and Mathematics. I also have a PhD in \ \ Biochemistry, with 4.5 years post-doctoral experience (mostly toxi cology/pharmacol ogy research). I am \ \ a Diplomat of the American Board of Toxicology, a certification confirming mastery of the specialty. \ \ I strive for excellence and my recent evaluations have been "exceeds expectations" or \ j "outstanding". I am a very motivated person, with papers in excellent journals such as Nature Genetics j i (first author) and PNAS. My Nature Genetics paper was central to our laboratory getting a $1.4 million i I i I grant subsequently and it was listed as one of the top research advances of the year by Neurology Today. j ) I \ This work was also a pivotal one in both the fields of mitochondrial and muscular dystrophy research that has led to successful human clinical trials. I am an expert in High Content Screening imaging and \\I l mitochondrial research. \ \ My independent initiatives have been pivotal to make my previous projects successful. I work well \ \ in a team format, but I also work very well independently. I have demonstrated leadership roles. I have \ ) very good problem-solving skills and I have initiated new projects at previous pharmaceutical companies. \ l I have excellent oral and written communications skills. I have presented my research at international \ j meetings. I have good equipment repair skills. I have experience with HCS and HTS laboratory j \ automation. I have supervisory skills experience. I have experience with patents, new product \ \ development and process development. \ i i i i i i i i i i 1 \ I have over 10 years work in product development and I have a great deal of experience in this \ '} area. I have provided a great deal of input into products for my past companies (technically and as a \ l market viewpoint). I even supervised implementing new processes that I designed into the production \ l facilities. I am extremely practical in business matters as they apply to research. j 1 \ Research expenditures (time and money) need to be focused on products that will make profit for j '} the company. Research decisions need to be market driven and based on what the customers will \ t purchase, so that the company can prosper. As a manager, I am demanding, but fair. I have always met \ j my goals and I often exceed them. I obtained the prestigious Highly Skilled Migrant Programme UK j i Visa while working for Pfizer. ( i i ( \ Summary; Risk assessments for pesticides experience, Toxicologist, PhD in Biochemistry, Nature & \ i PNAS publications, >10 years post-graduate experience as a scientist 14 years industrial research \ j experience, 4.5 years postdoctoral research experience, toxicology experience at US EPA, Pfizer, Cerep, j i and GSK (toxicology/pharmacology), BS degrees in Chemistry and Physics/Mathematics, experience ( \ with many different types of assays (chemical, biochemical and physical), product development and J \ production plant implementation experience, fluorescence microscopy assay expertise, High Content \ | Screening, Macrolide biochemistry. GSK work experience, Muscle Research experience, Mitochondria \ j research experience, Statistically Designed Experiments, Computer Programming, US Patent as first j 't author, Lipton experience, Interests/knowledge in Diabetes and Transplantation, Environmental testing, \ j "ISQ9000" skills. SDS-PAGE, Immuno-Assays, Graduate School GPA=3.9, EpiSuite OSAR Chemical j 1 Modeling Software, ICCYAM, Journal Editing experience, DABT Certification, PBPK, Process Chemist i \ experience, Highly Skilled Migrant Programme UK Visa, Senior Scientist in biotech | i i l Work Experience: ] S 1 \ Toxicologist, US Enviromental Protection Agency tUS EPAE 8 Years August 2, 2009-Present. Work | \ involved writing and reviewing hazard characterizations and risk assessments for herbicides, fungicides, \ \ insecticides, and toxic substances to protect the environment and the general public. Duties also involved j j critically reviewing tox studies or protocols, writing data evaluation records, presenting tox research at j i SOT meetings, interacting with the press, participating in QSAR evaluations and providing scientific i j guidance to in vitro tox assay development, as well as mitochondrial-based studies. I also am a member J Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00006 I I | of the ROCKS committee, which evaluates the structural properties of chemicals and residues in j i plants/animals. I was a co-author on a 20-page book chapter reviewing organotin toxicity and its j j reproduction/developmental/endocrine disruption effects. My farm experience with many chemicals, j ) chemistry, toxicology and physics backgrounds provide unique insights into the needs of the consumers, \ \ public, wildlife and manufacturers. I received an award for developing a physical chemistry model of \ \ exposure. I am also on the Risk Assessment Review Committee (RARC) which has the final evaluation \ \ of EPA risk assessments. I participated in a Scientific Advisory Panel on the pyrethroids. Presented 6 \ j times at SOT: mitochondrial toxins, organotin endocrine model, neurotoxicity signs, toxicology j i application of thermodynamics, organelle imaging toxicology, cancer biology models. Dermal, inhalation i I i I and gastro-intestinal policy work, as well as toxicity structural alerts and qualitative risk assessment j ) strategies. OECD dermal sensitization assay validation team. Risk Assessment Forum. FiazRATT \ \ committee co-chair. Lung Toxicity Project toxicology lead (Innovation Award). Focus risk assessment \ j committee, Structure Activity QSAR committee, Mentoring andtraining new staff j i i \ \ Cellular Toxicologist-Senior Scientist Cellumen. Inc.: 2.5 Years Nov. 1, 2006-March, 2009, Research j \ involved developing new test assays using advanced HCS imaging technology to assess drug toxicity and \ \ mechanism of action, representing company in booth at trade shows and overseeing collaborations with j j partner companies. Primary and tumor cell isolation/propagation for use in assay development. I j i developed and patented a panel of assays which was the major revenue producer for the company and < j was a senior level-researcher that contributed to major research decisions and policies in the company. I J \ supervised my own research associate, as well as co-supervised several others. Research also yielded a \ l publication on cellular systems biology and a US patent (first author). Trained and mentored staff, wrote j |SOPs, set policies, and QC of data. Laid off due to economic recession. j \ \ Toxicology Assay Consultant, GSK Pharmaceuticals 9 Months HTS Lab (Pliva Site, Zagreb, j \ Croatia): Feb. 1, 2006-Oct. 15, 2006 Research involved developing new test assays to assess drug \ l toxicity and cellular action (mostly antimicrobials and antibiotics) utilizing fluorescence plate readers, j | FACS and fluorescence microscopy. Research into alternate macrolide pharmaceutical applications, j t immunotoxicity assays, mitochondrial assays and effects on cells at the sub-cellular level were also < j performed. I supervised two research associates in the HTS laboratory. Research yielded two review J iiarticles on tox assay development guidance. I left when offered Cellumen position back in the USA. <i \ j Cellular and Biochemical Toxicologist, Pfizer Pharmaceuticals 3 Years, Sandwich Site (Kent j t England, Dec. 2002-Dec. 2005). Research involved developing new test assays to assess drug toxicity < j utilizing fluorescence microscopy and High Content Screening technology in the Safety j \| Sciences/Pharmacology department and in collaboration with Cerep and the University of Padova, Italy. \| l The first year of research was in Padova, Italy at the University developing muscle tox assays and the j j remaining two years were in Sandwich, England at the Pfizer Global Research Centre (supervised by j i SRG with Cerep funding). Research also involved optimizing High Content Screening microscopy i j technology for mechanism of action and toxicology studies for drug discovery. Supervision and training j I of 3 junior lab members was also involved. Research yielded a high-impact 25-page paper on HCS \ \ applications in toxicology with impressive concordance to human toxicity which has been highly cited j \ (Arch. Tox. 2006, cited 423 times). Many types of compounds were evaluated on the system such as \ I antibiotics, medications, pesticides, solvents, household chemicals, etc. The research was involved with j j animal reduction, refinement and replacement (the 3 R's and ICCYAM projects). I started this research | i while still in Italy during postdoctoral study (one year overlap period). Completed three full contracts and i I went to GSK. j s i jj I I Research Chemist, Lipton/Kind & Knox, Inc./DGF Stoess/Gelita 9 Years Chemist in research and j \ development laboratory. Research involved test method development and experiments/troubleshooting in \ \ the production facilities. Other work involved developing new products and improving existing products j j derived from collagen for the pharmaceutical, photographic and food industries. Implementing new j i technology, up-scaling laboratory research into the production facilities, and supervising laboratory i j interns was also performed. Kind & Knox is a division of DGF Stoess, the largest producer of medical- \ \ grade collagen and collagen-derived protein products in the world (previously owned by ( ... ..Lmton/Unijeyeu. j madejifisoptatiops tpJlig^gnemLmanageL...........................................................................I Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00007 I I | I have "IS09000" QA/QC skills, as well as statistical designed experiments experience. I have j i excellent skills of adapting quickly and determining which components of a process are critical and to j j find solutions to improve both efficiency and quality. I worked as a process scientist in a development j ) laboratory, transferring laboratory models into practical implementation on a large scale. I also have \ \ extensive experience in water treatment, purification and testing. I left to complete a PhD program. \ i1 IPost Doctoral Study, Paolo BernardiLaboratory2 Years (University ofPadova, Italy, Department of \ jBiochemistry andPathology): June 15,1999-June 2001.Supported byTelethon Fellowship/Grant j i #1141("Mitochondria asTargets ofPharmaceuticalIntervention inMuscle Disease"). Research i a i l involved the study of anesthetics and extra-cellular matrix protein knockout on skeletal muscle as models j ) I \ of muscular dystrophy. The study of the mitochondrial permeability transition/apoptosis in intact muscle cells, fibroblasts and hepatocytes was performed. The calcein-release method and the cytochrome c \\I i " j i release immunoassay were used to monitor the permeability transition in intact cells (normal vs i j cancerous), utilizing fluorescence microsopy and confocal microscopy, respectively. Calcium j ) measurement techniques/signaling (cytosolic and mitochondrial) were also performed in collaboration \ l with theTullio Pozzanlaboratory. Mostof the research was intoxicology areas. \ i1 I**s;Research yielded aProceedingsof theNational Academyof Sciences article on an epigenetic j I carcinogen and a Journal o fBiological Chemistry publication on anesthetic myotoxicity. j ( j i I Post Doctoral Study, Paolo Bonaldo Laboratory 2 Years (Department of Histology, Microbiology j ) I I and Medical Biotechnologies, University of Padova) June 2001-Dec. 2003. Supported by Telethon Grant #1201 ("Study Of Bethlem Myopathy Using Collagen 6 Knockout Mice As An Animal \jI j Model"). Research involved the study and histology of collagen VI knockout mice in as a model of j \ Bethlem/Ullrich Muscular Dystrophies. The mitochondrial permeability transition in intact muscle cells \ \ was monitored using TMRM fluorescence assays by fluorescence microscopy and confocal microscopy. \ ) Calcium signal transduction and calcium measurement techniques were also performed. Also, started \ I performing research for Pfizer while still in Italy during my postdoctoral study. j i i i i \ *Research yielded a Nature Genetics publication with myself as a first author and listed in Neurology \ \ Today as one of the top research advances of 2003. This research led to successful human clinical trials \ ) for a muscular dystrophy therapy, methods replicatedfor other diseases and cited 359 times.. i\ 1 \ Effluent Water Monitoring Consultant 4 Months (IBP Inc., Iowa, Kansas, Texas) Collected samples j \ of production plant effluents at various locations and waste water lagoons and tested them in the \ \ laboratory for industrial waste products that could adversely affect the environment. \ | t| l Skills: Toxicology risk assessment and data analysis, QSAR, ICCVAM, COOP disaster team, i j Fluorescence and confocal microscopy, High Content Screening microscopy, HPLC skills, Problem- | \ solving skills, Calcium testing, Protein purification/chemistry, Polymer chemistry, Affinity and Ion ( \ exchange chromatography, A wide range of chemical and physical testing assays, Primary cell isolation \ '} and culture (hepatocytes, skeletal muscle, fibroblasts, cardiac myocytes, etc.), Electrophoresis, Western ( f blotting, Electronic and mechanical equipment repair skills, Equipment modification skills, \ j Mitochondrial and permeability transition expertise, Mitochondria isolation/testing (heart, liver, kidney, j l muscle, invertebrates, etc.), Metabolism biochemistry and biochemical assays, Enzyme kinetics, Interests i l in structure/function relationships of compounds on biological systems, Computer skills and j I programming, Statistical designed experiments, Animal surgery, Invertebrate tox models, Biochemistry ( \ laboratory teaching, Research intern supervision, Team project research, Excellent English language j ') skills, "IS09000" skills (QA/TQM), Macrolide biochemistry, Muscle research experience, New Product \ f development, Process development, Computer skills (Excel, Word, PowerPoint, programming, etc.), \ j Company Representative at trade show booth, Scored very high on PA Forensic Scientist exam and the j I Environmental position exam, Environmental Chemistry laboratory instructor, Defibrillator/First Aid, ( j ToxSAC experience, Basic & Applied Myology Board Member, Highly Skilled Migrant Program UK j i Visa i i i i i i i Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00008 I I \ j Specialized Training: jaaaaooaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaOSbaai \j \ \ j High Content Screening Imaging Microscopy Training (3 weeks) Course covered in-depth the theory j \ and practical applications of simultaneous, multi-probe fluorescence microscopy in research and \ \ medicine. Cellomics, Inc. Pittsburgh, Pennsylvania, 2003 (updated in 2005) \ ( i \ I Ion Exchange Chromatographv/Technology Course 13 Days) Course covered applications and theory \ j of advanced ion exchange purification and separation methodsin industry and research. The focus was j \ on the purification of drinking water from hazardous materials.Illinois Water Treatment Co., Dearborn, \ \ Illinois \ I Membrane Senaration/Purification and Filtration Technology Course 13 Days) Course covered \ \ applications and theory of advanced membrane separation/purification/filtration technology in industry \ \ and medicine. Chicago, Illinois. \ i i i i I Statistical Design of Experiments 1T.J. Lipton. Inc.l Course covered the basics of designing < a i l statistically optimized experiments and data interpretation i i 1 \ ISO Quality Systems Covered the essentials of "IS09000" type of quality systems implementation and \ j auditing procedures j i \ IJS Patents Workshop fMIC. 3 Davsl Course covered the fundamentals of US patent concepts and \ | applications j i \ EpiSuite OSAR Chemical Modelling Course Structure analysis relationships software. US EPA. 2009 j i \ Toxicology Study Groups US EPA 2009-2010 and 2017 { i i t Ii Physiologically Based Pharmacokinetic fPBPKt Models in Risk Assessment SOT Meeting. 2011 <i t \ Grant Writing Workshop j i | Advanced Writing Training US EPA. 2011 | i \ Risk Assessment Training US EPA. 2011 j I 1t I Neurotoxicity Assessment Training US EPA 2012 i \ ! NIST Standards Workshop NIST 2013 | i i i i \I Alternative In Vitro Toxicology Testing for the 21st Century SOT Workshop. 2012 \\ S 1 jI NIH Nanomaterials Workshop NIH. 2013 Ij i j Practical Applications of Emerging Scientific Tools. ASCCT Symposium NIH. 2013 j ! ! Adverse Outcome Pathways Workshop NIH 2014 \ iii Primary Mitochondrial Disorders Workshop NIH 2014 jii i i i i i OECD OSAR Toolbox Training June 2017 i \ i i i \ ! \i Alternative Methods Toxicology Workshop IIVS July 2017 \i Ii ii i i Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00009 I I i -E--d-u--c-a--ti-o--n-:_ i\ \ \ j Bachelor o f Science Degree (Morningside College) j \ Major: Chemistry Minors: Physics, Mathematics \ \ Undergraduate Research involved interfacing normal laboratory equipment to computers. I was a \ \I laboratory instructor for an Environmental Chemistry class and an Electronics (Physics) class. \I 8 j \ PhD Degree: Biochemistry and Molecular Biology (Sanford School ofMedicine, GPA=3.9) j ) Doctoral research involved developing methods to protect vital tissues from hypoxia (i.e. transplantation \ \ conditions) or conditions of exposure to toxins. In particular, our laboratory sought to protect \ \ mitochondrial integrity and tissue/cell viability during conditions of hypoxia/transplantation, \ \ mitochondrial inhibition, toxic insults or stress. Most experiments involved toxicology, metabolism or \ j pharmacology research (>78 credit hours in toxicology research). Other projects during the doctoral j i program involved invertebrate toxicity models, protein folding/chaperone/collagen synthesis enzyme i I biochemistry and ethanol metabolism enzyme kinetics (i.e. aldehyde dehydrogenase). i I ***Research yielded a Biochemical Biophysical Research Communications article on the toxicity j j of aldehydes and a book chapter publication Prolyl Hydroxylase, Protein Disulfide Isomerase and Other | \ Structurally Related Proteins. i i ' i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i I ! ! I i I i I i I i I 1 I 1 1 I 1 i i i t I ! ! I i I i I i I i I 1 I 1 1 I 1 i i I I I ! ! I i I i I i I i Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00010 U N I V E R S I T Y OF SC II DAKOTA SAYFORD SCHOO: O'" '1!J VU \ " October 16,. 2012 Ms, Erfttany Juones Human Resources Specialist O, S. Environmental Protection Agency Human Resources Management Division--Branch. Research Ti tangle Parie North Carolina 27711 Dear Ms, Jones;:: IE:: W iliam A, Irwin. PhD, M I T Dr. William Irwin has asked feat I write regarding Ms application for a position with your organization. Will earned his PhD. in our Department of Biochemistry and Molecular Biology in 1999, Iwas chair of the department and a m em ber of Will's dissertation committee, The title of W ills dissertation was the "An investigation into the Protective Mechanisms of Fructose on Hpatocytes Daring Hypoxia". This w ork focused on the im pact of a variety of mitochondrial toxins th at induce hypoxia in mammalian, hpatocytes. Cyanide, rotenoae and aiitiiiiyda A all government-regulated pesti cides, damage hepatocyte mitochondria which results m hpatocyte death and ultimately liver failure. Will demonstrated that fructose can protect hepatocyte mitochondria fromtoxin damage, thereby preventing hepatocyte death. Will's research approaches and m ethods were the tools of biochemical toseology. The identification of fittetose's protection from the lo se effects of these compounds is applied tadcology. if I can provide additional infom iatioii please do not hesitate to contact me, Sincerely yours. Ronald Lindahl, PhD. Executive Dean Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00011 Patents: "Cellular Systems Biology Assays to Assess Human Toxicity Potential Utilizing Primary Rat Hepatocytes" (William Irwin, Larry Yemetti, Kate Johnston), Filed in USA and Europe (pending) Publications: Irwin, W., Bergamin, N., Sabatelli, P., Merlini, L., Megighian, A., Reggiani, C., Braghetta, P., Columbaro, M., Volpin, D., Bressan, G.M., Bernardi, P., Bonaldo, P., "Mitochondrial Dysfunction and Apoptosis in Myopathic Mice with Collagen VI Deficiency" (2003) Nature Genetics Vol. 35 (No. 4): 367-371 See also commentaries about this article: Rizzuto, R. The Collagen-Mitochondria Connection (2003) Nature Genetics Vol. 35 (No. 4): 300-301 From the Editor's Desk (2004) Matrix Biology Vol. 22: 519-520 Editors' Picks: Top Research Advances From 2003 (2004) Neurology Today Vol.4 (No. 1): 5- 6 Hayworth, J. "Mitochondria Play a Role in Disease (Biochemist William Irwin)" Sioux City Journal (2003) Hayworth, J. "Scientist Irwin Takes Studies To Italy" Sioux City Journal (2003) Kloehn, P., Soriano, M., Irwin, W., Penzo, D., Scorrano, L., Bitsch, A., Neumann, H-G., Bernardi, P. "Early Resistance to Cell Death and to Onset of the Mitochondrial Permeability Transition During Hepatocarcinogenesis With 2-Acetylaminofluorene" (2003). Proceedings o f the National Academy o f Sciences Vol. 100 (No. 17): 10014-10019 Irwin, W., Jelic, D., Antolovic, R. "Biomarkers for Drug Discovery: Important Aspects of in vitro Assay Design for HTS and HCS Bioassays" (2006) CROATICA CHEMICA ACTA 81 (1): 51-59 Vemetti, L., Irwin, W., Guiliano, K., Gough, A., Johnston, K., Taylor, D. "Cellular Systems Biology Applied to Pre-Clinical Safety Testing" Drug Efficacy, Safety, and Biologies Discovery: Emerging Technologies and Tools (Wiley & Sons, 2008) Irwin, W., Jelic, D., Antolovic, R. "Bio-Assays for Drug Safety and Mechanism Assessment: Design, Precautions and Integration" ("Medicinal Chemistry in Drug Discovery" , July 2009) Doherty, J., Irwin, W., "Organo-Tins: Reproductive and Developmental Effects in Mammals", US EPA sponsored, Manuscript published in the book "Reproductive and Developmental Toxicology", Elsevier, February 2011 Irwin, W., Fontaine, E., Penzo, D., Bernardi, P., "Bupivacaine Myotoxicity Is Mediated By Mitochondria" (2002). Journal o fBiological Chemistry Vol. 277(No. 14): 12221-12227. Irwin, W., Gaspers, L., Thomas, J., "Inhibition of the Mitochondrial Permeability Transition by Aldehydes" (2002). Biochemical Biophysical Research Communications Vol. 291 (No. 2): 215-219 Noiva, R., Onodera, S., Schwaller,M., Irwin,W. "The Peptide Binding Site of Protein Disulfide Isomerase" pp. 369-395. In Prolyl Hydroxylase, Protein Disulfide Isomerase and Other Structurally Related Proteins (1998), Editor Norberto Guzman, Marcel Dekker, Inc. New York O'Brien, P., Irwin, W., Diaz, D., Howard-Cofield, E., Bernardi, P., et al "High Concordance of DrugInduced Human Hepatotoxicity With in vitro Cyto-Toxicity Measured in a Novel Cell-Based Model Using High Content Screening" (2006). Archives o f Toxicology: 2006 Sep;80(9):580-604 Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00012 I I | Slaughter, M., Hougham, C., Hitchcock, J., Potter, A., Brain, P., Irwin, W., "A Medium-Throughput, j i Sensitive in vitro Screen for Chronic Cyto-Toxicity Assessment of Nucleoside Analogues", j j Manuscript in preparation j i i \ j Irwin, W., Gaspers, L., Thomas, J., "Fructose Protects Hepatocytes During Hypoxia or Toxin J \ Exposure by Inhibition of the Mitochondrial Permeability Transition". Manuscript in preparation \i \ j Affiliations: American Board o f Toxicology (ABT), Society o f Toxicology (SOT),Physics Honor j I Society, Mathematics Honor Society, American Chemical Society, A B T < j Standards o f Knowledge Committee, SOT National Capital Area Chapter, SOT \ '} In Vitro Toxicology Specialty Section (\ \ ) I 8 Languages: English (fluent), Italian (essential), Spanish (basic), Croatian (basic) j\I \ ImdteiLSeminar&i. | i I American Chemical Society Annual Meeting (August, 2017), "Qualitative Risk Assessment i | Strategies" j lUS EPA (October, 2016), "Critical Aspects of In Vitro Assay Design, Analysis and Integration" j \ \SOT Meeting (March, 2015), Ask An Expert Program: "In Vitro Toxicology Assay Design" [ j (| I SOT Meeting (March, 2014), Ask An Expert Program: "Mitochondrial Toxicology" j i i i i i US EPA (Oct. 2, 2012), "Important Aspects of In Vitro Assay Design and Interpretation" < i i t \US EPA (May 25, 2010), "Mitochondrial Toxicities and Interactions With Other Organelles" \i i II Notre Dame School of Medicine (May 29, 2009) "Organelle Pathologies in Disease States" j\ i \ Stem Cell Research Center, University of Pittsburgh (Feb. 9, 2009) "Mitochondrial andSR Pathologies j ) t in Muscular Dystrophy" \i i l Croatian Society of Biochemistry Annual Meeting (Oct. 3, 2006, Vodice, Croatia),"High Content j i Screening Imaging Applications in Toxicology and Pharmaceutical Discovery" < i i t \ Becton Dickinson (August, 2006) "High Concordance of HCS-Based Toxicity Assays With Human \ \ Drug Toxicity" | i i ii i Cellumen, Inc. (August, 2006) "High Content Screening Applications in Drug Discovery Programs" i i i i i \ Cellomics, Inc. (August, 2006), "Human Drug Toxicity Concordance With High Content Screening i > In Vitro Assays" { i | i| l University of Iowa Medical School (Aug. 10, 2006) "Mitochondrial Research: Experimental Design, j j Assay Precautions and Data Interpretation" | i i \ University of Iowa Medical School (Aug. 9, 2006) "High Content Screening Fluorescence Microscopy j } Applications in Medical Research" \ i } University of Iowa Medical School (K. Campbell sponsor, Aug. 9, 2006) "In Vivo and In Vitro \ l Characterization of the Collagen VI Knockout Mouse Model of Muscular Dystrophy" i ! i \ i Croatian Genetic Society, (May 17, 2006, Zagreb, Croatia) "Use of Macrolides as Discovery Tools in i \ Medical Research: Muscular Dystrophy Applications" \ Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00013 Pfizer Pharmaceuticals, Safety Sciences (October 24, 2005, Sandwich, England) "Organelle Pathologies in Muscle Disease" High Content Screening Conference (October 19, 2005, Le Mridien, London, England) "Predicting Drug-Induced Hepatotoxicity With in vitro Cyto-Toxicity Assays: High Content Screening Methods" Croatian Society of Biochemistry and Molecular Biology (September 2005, Zagreb, Croatia) "The Unexpected Organelle Pathology in Collagen VI Deficiency Muscular Dystrophies" Pfizer Pharmaceuticals (March 2005, Sandwich, Kent, England) "The Role of Mitochondria in Carcinogenesis" Sanford School of Medicine (February 28, 2005) "The Unexpected Organelle Pathologies in Collagen VI Deficiency Muscular Dystrophies" Pfizer Pharmaceuticals (May 2004, Sandwich, Kent, England) "High Content Screening MultiChannel Fluorescence Microscopy Applications in Toxicology" Pfizer Pharmaceuticals (March 2004, Sandwich, Kent, England) "Important Biochemical and Metabolic Considerations in Muscle Diseases and Their Therapies" Pfizer Pharamaceuticals (November 2003, Sandwich, Kent, England) "Mitochondrial Membrane Potential Measurement Applications in Toxicology, Techniques and Precautions" University of Padova, School of Medicine (October 2003, Padova, Italy) "High-Content Screening Methods: Utilizing Coherent Multi-Probe Fluorescence Microscopy to Monitor Simultaneous Subcellular Events" Pfizer Pharmaceuticals (May 15, 2003, Sandwich, Kent, England) "Anesthetic Toxicology: Calcium And Mitochondrial Roles In Muscle Pathology" Padova Foundation of Organ Transplantation (March 20, 2003, Padova, Italy) "Organ Transplantation: Important Metabolic and Biochemical Considerations" Sanford School of Medicine (September 28, 2001): "An Animal Model of Human Bethlem Myopathy: Muscle Characterization of Collagen VI Knockout Mice" NovaSite Pharmaceuticals (September 21, 2001, San Diego, California,): "Muscle Characterization of Collagen VI Knockout Mice: An Animal Model of Human Bethlem Myopathy" University of Colorado, Health Sciences Center (December, 1999, Denver, Colorado): "Fructose and Glyceraldehyde Protection of Hepatocytes During Hypoxia Is Mediated by Mitochondria" University of North Carolina (December 1999, Chapel Hill, North Carolina): "Fructose Protects Hepatocytes During Hypoxia by Inhibition of the Mitochondrial Permeability Transition" DGF Stoess, Inc. (February, 1993, Sioux City, Iowa) "The Biochemistry of Collagen Proteins and Implications in Various Pathologies" Sanford School of Medicine (January 1993): "Collagen Biochemistry in Health and Disease" Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00014 Seminars: London School of Hygiene and Tropical Medicine (May 22, 2009) "High Throughput Screening Assay Applications in Tropical Disease Research" Toxicology 2003 Conference (Dec. 9 2003, London, England) Predicting Drug-Induced Human Hepatotoxicity With In Vitro Cytotoxicity Assays University of Padova, Department of Medical Biotechnology (May 2003, Padova, Italy): "Collagen VI, Calcium and Mitochondrial Roles In Bethlem Myopathy" University of Padova, Department of Microbiology (December 2002, Padova, Italy): "Important Metabolic Considerations in Muscle Diseases for Therapeutic Intervention" University of Padova, Department of Histology (May 2002, Padova, Italy): "An Animal Model of Human Bethlem Myopathy: Characterization of the Pathological Defects in the Skeletal Muscles of Collagen VI Knockout Mice" University of Padova, Department of Biomedical Sciences (July 2001, Padova, Italy) "Ullrich Muscular Dystrophy Is Caused By Mutations In The Collagen VI Genes" University of Padova, Department of Medical Biotechnology (May 2001, Padova, Italy): "The Role of Mitochondria in Muscle Cell Death" University of Padova, Department of Biomedical Sciences (March 2000) "HIV-1 Mediates Apoptosis By Its Proteins Inducing The Mitochondrial Permeability Transition" University of Padova, Department of Biomedical Sciences (September 1999, Padova, Italy): "Fructose Protects Liver During Hypoxia By Its Metabolite Glyceraldehyde Protection of Mitochondrial Function" Sanford School of Medicine (June 1999): "An Investigation Into the Protective Mechanisms of Fructose To The Liver During Hypoxia" Sanford Medical School, Department of Biochemistry and Molecular Biology (January 1998): "Membrane Transporters That Lack Protein Components" Sanford School of Medicine (October 1997): "Artificially-Gated Pores: Designer Pore Applications in Cancer Chemotherapy, Cryopreservation and Biosensors" Sanford School of Medicine (January 1997): "Immunophilins: Protein Folding Roles in Signal Transduction, Vision, Secretion and AIDS" Sanford School of Medicine (December 1996): "Prion Proteins and Disease" Sanford School of Medicine (March 1996): "Gerontogenes, Diet, Free Radicals and Aging: Factors That Affect the Lifespan of an Organism" Sanford School of Medicine (October 1995): "The Involvement of Mitochondria in Cell Life and Programmed Cell Death" Sanford School of Medicine (May 1995): "How Does Fructose Protect Liver Tissue From Hypoxia?" Sanford School of Medicine (October 1994): "The Role of Mitochondria in Ischemia-Reperfusion Injury" Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00015 Sanford School of Medicine (April 1994): "Investigation Into the Role of the Protein Disulfide Isomerase Subunits in Prolyl Hydroxylase Activity" Meetings Presentations: American Chemical Society Annual Meeting (August 2017): "Adverse outcome pathwaysa mechanistic approach for future risk assessments" American Chemical Society Annual Meeting (August 2017): "In vitro metabolomics as alternative testing strategy for predicting adverse outcome pathways of the exposome" Mitochondrial Health Meeting (June 2017, Arlington, VA) Poster Presented: "Mitochondrial Involvement in Carcinogenesis" Society of Toxicology Meeting (March 2017, Baltimore MD) Poster Presented: "Mitochondrial Roles in Tumorigenesis" Mitochondrial Biology Symposium (NIH, Bethesda, MD, May 19-20, 2016) Poster Presented: "Oranelle Imaging Toxicology: Utilizing Coherent Multi-Probe Fluorescence Microscopy to Monitor Mitochondrial Health and Other Simultaneous Sub-cellular Events" Future Tox III, Society of Toxicology Meeting (November 2015, Crystal City, VA) Poster Presented: "Utilizing Coherent Multi-Probe Fluorescence Microscopy to Monitor Simultaneous Sub-cellular Events" Society of Toxicology Meeting (March 2015, San Diego, CA) Poster Presented: "Organelle Imaging Toxicology" Society of Toxicology Meeting (March 2014, Phoenix, AZ) Poster Presented with Professor Don Fox: "Compound-Induced Bioenergetics Alterations: Relevance to Pathophysiology" Society of Toxicology Meeting (March 2012, San Francisco, CA) Poster Presented: "Functional Observational Battery in Perspective" Society of Toxicology Meeting (March 2011, Washington, DC) Poster Presented: "Organotin Toxicology: A Novel Mitochondrial Nernst Model" Society of Toxicology Meeting (March 2010, Salt Lake City) Poster Presented: "The Role of Mitochondria In Toxicology" World Pharmaceutical Congress (May 2008, Philadelphia) Represented Cellumen, Inc at trade booth High Content Analysis 2007 (Jan. 2007, San Francisco) Represented Cellumen, Inc. at trade booth Croatian Biophysics Congress (September 2006 Rovinj, Croatia) Poster Presented: "Non-Radioactive Fluorescence-Based Cell Quantitation Assay Development" Society For Biomolecular Screening Meeting (September 2005, Geneva, Switzerland) Poster Presented: "An In Vitro Oxidative Stress Biomarker Assay For Drug Toxicity Screening" Telethon Convention (2005, Salsomaggiore Terme, Italy) Poster Presented: "Therapeutic Intervention in Muscular Dystrophy Targeting Mitochondria" Bemardi, P., Irwin, W., Angelin, A., Bergamin, N., Sabatelli, P., Merlini, L., Megighian, A., Reggiani, C., Braghetta, P., Columbaro, M., Volpin, D., Bressan, G.M., Bonaldo, P. Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00016 New R&D Opportunities Forum (December 9, 2004, Sandwich, England) Poster Presented Poster Presented: Low-Dose Enhancement Drug Responses in In Vitro Toxicity Assays: Detecting and Modelling Hormesis Effects of Drugs Ethical Innovation in the Laboratory (Sept. 21, 2004, Sandwich, England) Poster Presented. Utilizing In Vitro, Human Tumor Cell Line-Based Fluorescence Microscopy Screening Assays (High Content Screening) to Reduce Animal Testing in Drug Safety Assessments. The intent was to refine, reduce and replace animal testing (the 3 R's) with advanced in vitro toxicology models and ICCVAM initiatives. Biomarkers Forum (April 29, 2004, Sandwich, England) Poster Presented. Evaluation of Fluorescence Microscopy-Based In Vitro Safety Assays (High Content Screening) For Predicting Drug Toxicity in Humans Telethon Convention (2004, Italy) Poster Presented: "Mitochondrial Intervention in Muscle Disease" Bemardi, P., Irwin, W., Angelin, A., Bergamin, N., Sabatelli, P., Merlini, L., Megighian, A., Reggiani, C., Braghetta, P., Columbaro, M., Volpin, D., Bressan, G.M., Bonaldo, P. Group Italian Bioenergetics Biophysics Congress (2003, San Daniele, Italy) Oral Presentation'. "Lack Of Collagen VI Causes Mitochondrial Dysfunction And Calcium Dysregulation In Skeletal Muscle" Irwin, W., Bergamin, N., Sabatelli, P., Merlini, L., Megighian, A., Reggiani, C., Braghetta, P., Columbaro, M., Volpin, D., Bressan, G.M., Bemardi, P., Bonaldo, P. Telethon Convention (2003, Italy) Poster Presented: "Study of the Mitochondrial Pathogenesis of Bethlem Myopathy Using COL6A1 Knockout Mice as an Animal Model"." Bernardi, P., Irwin, W., Angelin, A., Bergamin, N., Sabatelli, P., Merlini, L., Megighian, A., Reggiani, C., Braghetta, P., Columbaro, M., Volpin, D., Bressan, G.M., Bonaldo, P. Group Italian Bioenergetics Biophysics Congress (2001, Ancona, Italy) Oral Presentation'. "An Animal Model of Human Bethlem Myopathy: Characterization of the Pathological Defects in the Skeletal Muscles of COL6A1 Knockout Mice" Irwin, W., Bergamin, N., Sabatelli, P., Merlini, L., Megighian, A., Reggiani, C., Braghetta, P., Volpin, D., Bressan, G.M., Bemardi, P., Bonaldo, P. Group Italian Bioenergetics Biophysics Congress (2000, Friuli, Italy) Oral Presentation: "Mitochondria in Muscle Cell Death by Bupivacaine" Irwin, W., Fontaine, E., Bemardi, P. South Dakota Academy of Sciences Congress (1996, Rapid City, South Dakota) Oral Presentation'. "Fructose and Its Metabolite D-Glyceraldehyde Protect Hepatocytes During Hypoxia" South Dakota Academy of Sciences Congress (1995, Madison, South Dakota) Oral Presentation'. "Investigation Into the Protective Mechanism of Fructose During Hypoxia" Keystone Symposia: Mitochondria and Pathogenesis (2002, Keystone USA). Poster Presented: "Mitochondrial Dysfunction in Muscle Fibers From Collagen VI Null Mice". Irwin, W., Bergamin, N., Sabatelli, P., Merlini, L., Megighian, A., Reggiani, C., Braghetta, P., Columbaro, M., Volpin, D., Bressan, G.M., Bemardi, P., Bonaldo, P. Telethon Convention (2002, Riva del Garda, Italy) Poster Presented: "Study of the Pathogenesis of Bethlem Myopathy Using COL6A1 Knockout Mice as an Animal Model". Irwin, W., Bergamin, N., Sabatelli, P., Merlini, L., Megighian, A., Reggiani, C., Braghetta, P., Columbaro, M., Volpin, D., Bressan, G.M., Bemardi, P., Bonaldo, P. Group Italian Bioenergetics Biophysics Congress (2001, Ancona, Italy) Poster Presented: "Mitochondrial Changes During Chronic Feeding With the Hepatocarcinogen Acetylaminofluorene". Klohn, P., Soriano, M., Irwin, W., ., Bitsch, A., Neumann, H-G., Bemardi, P. Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00017 I I | Telethon Convention (2001, Riva del Garda, Italy) Poster Presented: "Study of the Pathogenesis of j I Bethlem Myopathy Using COL6A1 Knockout Mice as an Animal Model". Irwin, W., Bergamin, N., j j Sabatelli, P., Merlini, L., Megighian, A., Reggiani, C., Braghetta, P., Volpin, D., Bressan, G.M., j I Bemardi, P., Bonaldo, P. < i i \ \ Telethon Convention (2001, Riva del Garda, Italy) Poster Presented: "Mitochondria as Targets of \ \ Pharmaceutical Intervention in Muscle Cell Death" Irwin, W., Fontaine, E., Penzo, D., Bemardi, P. \ i ( i i \ Group Italian Bioenergetics Biophysics Congress (2000, Friuli, Italy) Poster Presented: "Modulation of \ \ the Mitochondrial Permeability Transition at the P Site". Kloehn, P., Soriano, M., Irwin, W., Bitsch, \ ) A., Neumann, H-G., Bernardi, P. \ t i \ j Frontiers of Mitochondrial Research Congress (2000, Albany, USA) Poster Presented: "The Role of j i Mitochondria in Muscle Cell Death" Irwin, W., Fontaine, E., Penzo, D., Bernardi, P. i i i ( \ Telethon Convention (2000, Rimini, Italy) Poster Presented: "Study of the Pathogenesis of Bethlem \ I Myopathy Using COL6A1 Knockout Mice as an Animal Model". Irwin, W., Bergamin, N., Sabatelli, j II P., Merlini, L., Megighian, A., Reggiani, C., Braghetta, P., Volpin, D., Bressan, G.M., Bernardi, P., jI i Bonaldo, P. ( i i t \ Telethon Convention (2000, Rimini, Italy) Poster Presented: "Therapeutic Intervention in Muscle Cell \ I Death By Mitochondrial Modulation" Irwin, W., Fontaine, E., Bernardi, P. ( i i i i ) Telethon Convention (1999, Rimini, Italy) Poster Presented: "Mitochondria as Targets of \ \ Pharmaceutical Intervention in Muscle Cell Death" Irwin, W., Fontaine, E.,., Bernardi, P. \ t I Frontiers of Mitochondrial Research Congress (September 1998, Albany, USA) Poster Presented: ( j "Fructose Protects Hepatocytes During Hypoxia by Inhibition of the Mitochondrial Permeability | i Transition" Irwin, W., Thomas, J. ( i i t \ American Society of Biochemistry and Molecular Biology Meeting (August 1997, San Francisco, USA) \ t Poster Presented: "Fructose Protection of Hepatocytes During Hypoxia and the Mitochondrial ( \I Permeability Transition" Irwin, W., Thomas, J. )I ! \ American Society of Biochemistry and Molecular Biology Meeting (1996, New Orleans, USA) Poster \ \i Presented: "Protection of Hepatocytes by Fructose During Hypoxia" Irwin, W., Thomas, J. \ i i I ! ! I i I i I i I i I 1 I 1 1 I 1 \ i i t I ! ! I i I i I i I i I 1 I 1 1 I 1 \ i I I I ! ! I i I i I i I i Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00018 Mary Manibusan, Senior Managing Toxicologist 1150 Connecticut Ave., NW Washington, DC 20005 (202) 772-4926 mmambiKanpexponentcom Dear Sir or Madam, December 13, 2015 It is my great pleasure to recommend Dr. William Irwin for a position with your company. I had the .honor o f hiring Dr.. Irwin into the USEPA Office of Pesticide Programs when I had served as the Chief o f the Toxicology and Epidemiology Brandi. As a new hire, I immediately recognized Dr, Irwin's potential as a .key contributor and future leader of the Office of Pesticide Programs, During the years that followed. Dr. Irwin lias not only met my expectations, but exceeded them at many different levels. He has been a key contributor to the pyrethroid FXFRA Scientific Advisory Panel meetings due to Ms direct experience in Pharma with sodium channels; this is an important project for the Agency. As a technical reviewer, he has served as a member of the Residue Of Concern Knowledge based Subcommittee.. Quantitative Structure Actit ity Relationship and Risk Assessment Review Committee and .has performed the many functions of a highly skilled and experienced risk assessor,. The Office of Pesticide Programs has some challenging chemicals, mciwding Chlorpyrifos, Amitraz, Dkanifea and Dr. Irwin has contributed to these excellent assessments. In total, he has given, six unique presentations at SOT representing MED. served as a representative on tire Scientific Integrity Committee and wrote a chapter on organotis pesticide endocrine disruption in a development and reproduction book. Dr, Irwin has a unique background that includes a PhD in Biochemistry and ideal experience for mode of action investigations. I highly recommend Dr, Irwin for a technical leadership position within your company and organization. Sincerely, Mary Manibusan, Former Director of the Endocrine Disrupter Screening Program Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00019 December 1,2015 To Whom St May Concern: lam w riting this letter o f reference for Or. William Irwin, Dr, Irwin is currently employed by the Health Effects Division o f EPA's Office o f Chemical Safety and Pollution Prevention and works in the capacity o f toxicologist. In his current position, Dr, Irwin has made many contributions to the agency, A few o f bis notable achievements are listed below: M itochondria! toxicology expert (models validated In clinical trials! * In vitro toxicology expert (assays implemented into ToxCASTj Editor o f a toxicology journal -DA8T board certification in toxicology * Key contributor to the pyrothroid Science Advisory Pane! due to experience w ith sodium channels, an im portant project fo r the agency M em ber o f the several HED peer review committees Served as lead toxicologist on several complex pesticide active ingredients CSave 5 presentations at SOT representing HED * Served as representative on the Scientific Integrity Committee * W rote a book chapter m organotin pesticide endocrine disruption W illiam Is a valuable m em ber o f HED. Although I am: not his first " line supervisor, j am aware o f bis co ntribu tion s to th e organization. As bis Division Director, I see W illiam as a highly intellig en t individual w ith scientific expertise in toxicology. William is a dedicated and hard-w orking scientist w ho o fte n p u t bis personal life on bold to w ork on issues o f scientific im portance. Dr. Irwin holds himself and those around him to high standards, and takes great care in his work, Perhaps m ost im portantly, W illiam is a curious and creative scientist w ho likes to investigate new approaches and m ethods. He is very p roficient w ith technology and his celt biology training, specifically in m itochondriaSfunction, was very valuable to much o f his w ork in HED, Based on all the above factors, I recommend Dr.lrwin fo ra scientific position. Sincerely, Dana Vogel, Director, Health Effects Division, BB/OCSBB/DSEBA Sierra Club v. EPA 18cv3472 NDCA Attachments Prod 1 ED 002061 00039344-00020