Devin Michael Wolfe

Seasoned Principal Scientistt with discovery-oriented mindset, strong program management, and team leadership skills bolstered by broad expertise advancing small molecule approaches to rare neurological, metabolic and lysosomal storage diseases. Decisive project leader with proven track record identifying development candidates and optimizing transfer to contract research facilities. Experienced investigator with high EQ who effectively communicates rationale and methodology of scientific endeavors to key stakeholders. Manages team of 3 scientists and technicians. Outstanding technical and relationship management knowledge.

• Member, American Association for the Advancement of Science
• Member, American Society of Gene and Cell Therapy
• Member, American Society for Bone and Mineral Research

• Devin is a very intelligent and talented scientist. Our sickle cell program would not have advanced without him…I cannot say enough good things about his leadership, his detail and quality science, and how great it is to work with him day to day.
• Devin promotes the culture I strive to build in the group, which is that all our scientists need to produce results at the bench.
• I expect great things from Devin in the years to come. He continues to be a role model by being productive on a daily basis.
• I could not have asked for a better mentor… Devin has been the most supportive person… he is fiercely loyal to the people he represents

• Qualitative & Quantitative Methods
• Biochemical Assays (Development, Training, & Transfer)
• Study Design & Analysis
• Building & Leading R&D Teams
• Laboratory Management & Compliance

• Nucleic Acid Purification
• Molecular Cloning
• Gel Electrophoresis (Agarose) | SDS-PAGE ELISA | Immunoblotting
• Immunocytochemistry
• Magnetic Chromatography
• Confocal / Epifluorescent Microscopy

• Cell Toxicity / Cell Visibility Assays
• Tissue Culture | Cell Culture
• In Vitro Assays
• In Vivo Protein Functionality Assays
• Protein Isolation/Interaction Analysis
• Post-Translational Modification
• In Silico Analyses

• Relay Therapeutics, Cambridge, MA, Principal Scientist, 04/2021, 09/2023, As the first rare disease SME hired by Relay, played a key role in bringing critical assays on-line in house for 2 currently undisclosed Genetic Disease programs, as well as provided significant guidance on program strategy. Hired and developed a team to execute important POC and MOA studies, as well as developed additional orthogonal assays and animal models for key in vivo pharmacological studies. Scientific Leadership: Appointed co-project lead of one genetic disease program and biology lead of another. Established key assays and screening cascades for lead optimization to deliver on tight program timelines. Utilized expertise in rare diseases to internalize several enzymatic assays, as well as implemented a high content imaging system for assessing localization of a targeted protein in response to potential therapeutic compounds. Developed and oversaw execution for the biology strategy for the program up to DRF nomination Mentored and managed multiple direct reports, from RA through PhD level scientists
• Target Acceleration, Provided essential data for advancement of one project within 6 months of joining the company and played a pivotal role in obtaining PD and efficacy data in vivo. Developed an alternate strategy for in vivo model development using AAV after CRISPR model timelines were significantly extended, enabling in vivo POC to occur ~ 1 year faster than expected.
• Sanofi, Framingham, MA, Principal Scientist, lab head, 03/2020, 03/2021, Lead team of scientists charged with identifying, characterizing, and validating potential therapeutic targets, focusing on rare lysosomal and musculoskeletal diseases. Developed and managed a team that established POC assays and models for target validation, as well as designed and developed high throughput screening strategy for identifying small molecule inhibitors of validated targets. Scientific Leadership: Appointed Lab Head with 5 direct reports Utilized expertise in Lysosomal Storage Disorders to drive early discovery projects utilizing novel therapeutic approaches in LSDs. Developed scientific strategy, including key go/no go decision points, screening cascades and experimental design for a pre-clinical program targeting CNS and skeletal abnormalities in Hurler Disease. Concomitantly was the project lead on a novel program aimed at treating a rare form of osteopetrosis. Oversaw the successful identification of key hematopoietic indicators of anemia in the disease as well as worked with experts in bone biology to identify model systems for assay development. Provided important strategic input on departmental priorities and critical business continuity procedures during COVID pandemic, thus enabling the team to continue in progressing through key internal checkpoints. Developed direct reports, fostering a cohesive team environment, empowering the team to drive key studies and enabling organizational visibility for direct reports.
• Sanofi, Framingham, MA, Senior Scientist, 2015, 2020, Lead team of scientists charged with evaluating, characterizing, and validating potential therapeutic targets for investigations focused on rare diseases. Develop and manage team, establish assays and models for target validation, and present findings to influential stakeholders internally. Scientific Leadership: Appointed Sickle Cell Disease (SCD) project lead with team of 2 directs/10 indirects. Established lead-finding strategy, discovery flowchart, and timelines on program that exceeded expectations. Leveraged expertise in oxygen-binding analyses to expedite understanding of MOA, devised screening cascade and series of assays to test, and moved from development candidate through validation in 9 months. Gained valuable insight and experience into development of small-molecule screens to advance discovery projects and inform R&D investment/prioritization decisions. Utilized LSD experience to drive external collaboration efforts on non-viral gene therapy approaches in Pompe disease, a disease affecting primarily skeletal musculature. Cross-Functional Collaboration: Nurtured strong, productive relationships with disease-area experts and other interdisciplinary partners, fostering culture of excellence on the bench to galvanize pipeline innovation. Target Acceleration: Joined gene therapy immune evasion program that was struggling to advance and instituted successful turnaround agenda, instilling renewed rigor and focus. identified stability issues with encapsulated AAV in water, and drafted exemplary report that was presented to co-sponsor, Sagetis Biotech. Target Acceleration: Lead investigation for rare, potentially fatal metabolic syndrome, that despite an inability to identify a viable therapy lead to the characterization of 10-15 mutations, and the development of high-throughput screens for potential therapeutic candidate identification.
• Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, Post-Doctoral Assistant Research Scientist, 2009, 2015, Performed drug screening and development investigations into pharmacological restoration of elevated lysosomal pH, and autophagy by extension, in familial Alzheimer’s models. Developed weekly reports and presentation for principal investigator Dr. Ralph A. Nixon. Analyzed efficacy and toxicity in FDA-approved compounds with industry partner Takeda Pharmaceuticals. Efforts resulted in 5 publications and a patent. Assay Design: Joined study in early phases, contributing expertise in lysosomal biology to introduce and refine new methods for accurate measurement of lysosomal acidification and ionic content. Co-developed assays for assessing efficacy of therapeutic agents on Familial Alzheimer’s Disease (FAD) models. Protein Identification: Developed new study protocols, bioassays, and target validation methods, including high-throughput methods for measuring lysosomal pH using 96-well plates and spectrofluorometry. Industry Collaboration: Appointed lead scientist on study to identify novel lysosomal modulatory compounds with Takeda Pharmaceuticals. Acquired significant experience presenting and collaborating with senior-level scientists and research directors in academic and industry settings. Target Discovery: Uncovered class of compounds capable of restoring lysosomal acidification in an AD cell model via introduction of chloride transport, which re-acidifies lysosomes and restores pathway degradation.
• University of Rochester, Rochester, NY, Graduate Student, 2004, 2009, Planned/prioritized development and qualification of bioassays to study protein implicated in Batten disease: Btn1p, a S. cerevisiae CLN3 homolog. Guided growth and performance of team comprising 3 undergraduate students and maintained lab operations in compliance with laboratory GLP/GMP. As lab mentee under Principal Investigator Dr. David Pearce, co-authored 4 publications based on cutting-edge research at intersection of cell biology, molecular, and biochemical approaches. Leadership: Developed and mentored undergraduate students. Set goals, monitored performance, and provided guidance towards advanced academic and industry careers. Protein Quality Control: Modeled protein deficits in eukaryotic systems. Published review article in Neuromolecular Medicine emphasizing importance of yeast in investigation of proteins implicated in channelopathies. Assay Design: Identified and quantified pH-dependent localization in Btn1p, homolog of human gene CLNE mutated in Juvenile Neuronal Ceroid Lipofuscinoses.

• Cummings, S., Johnson, J., Taylor, K., Wolfe, D., Moreland, R., Yandle, E., Ryan, S., Cao, J., Ying, X., Rao, S., Thurberg, B., and Bangari, D., Progression of Tissue and Clinical Pathology in the Townes Knockout Transgenic Mouse Model of Sickle Cell Disease. Biology Open Under Review
• Lee, J.H., Wolfe, D.M., et al., Presenilin-1 mutation or loss disrupts ClC-7 delivery to lysosomes: reversal by ß2 adrenergic agonists restores lysosome acidification and autophagy J Mol Bio 2020 Apr 3;432(8):2633-2650
• Lee, J.H., McBrayer, M.K., Wolfe, D.M., Haslett, L.J., Kumar, A., Sato, Y., Mohan, P., Coffey, E.E., Kompella, U., Mitchell, C.H., Lloyd-Evans, E., Nixon, R.A. Presenilin maintains lysosomal Ca2+homeostasis by regulating vATPase mediated lysosome acidification Cell Rep. 2015;12(9):1430–1444.
• Wolfe, D.M., Lee, JH., Kumar, A., Lee, S., Orenstein, S., and Nixon., R.A. Autophagy failure in Alzheimer’s disease and the role of defective lysosomal acidification. Eur J Neurosci. 2013 Jun ;37(12):1949-61
• Wolfe, D.M. and Nixon, R.A. Autophagy Failure in Alzheimer’s disease and Lysosomal Storage Disorders: A Common Pathway to Neurodegeneration? Autophagy of the Nervous System. World Scientific Publishing (ed. Yue, Z and Chu, C).
• Wolfe, D. M., Padilla-Lopez, S., Phillips-Vitiello, S and Pearce D. A. pH-Dependent Localization of Btn1p in the Yeast Model for Batten Disease. Dis. Mod. Mech. (2011) Jan;4(1):120-5
• Lee, JH., Yu, WH., Kumar, A., Lee, S., Mohan, PS., Peterhoff, CM., Wolfe, DM., Martinez-Vicente, M., Massey, AC., Sovak, G., Uchiyama, Y., Westaway, D., Cuervo AM., and Nixon RA. Lysosomal Proteolysis and Autophagy Require Presenilin 1 and Are Disrupted by Alzheimer-Related PS1 Mutations. Cell. 2010 Jun 25;141(7):1146-58
• Schmidt, K., Wolfe D.M., Stiller, B., and Pearce D.A. Cd(2+), Mn(2+), Ni(2+) and Se(2+) toxicity to Saccharomyces cerevisiae lacking YPK9p the orthologue of human ATP13A2., Biochem Biophys Res Commun. 2009 May 29;383(2):198-202.
• Phillips-Vitiello, S., Wolfe, D.M., and Pearce, D.A. Yeast strains lacking Btn1p require tight control of intracellular arginine levels., Hum Mol Genet. 2007 May 1;16(9):1007-16
• Wolfe, D.M. and Pearce, D.A. Channeling in yeast: Yeast as a model for channelopathies. Neuromolecular Med. 2006;8(3):279-306.