Corinne E. Augelli-Szafran, Ph.D, Director of LEAD
Corinne E. Augelli-Szafran, Ph.D. at Harvard Medical School and Brigham and Women’s Hospital. Dr. Augelli-Szafran spent seventeen of her twenty years of industrial experience at Parke-Davis and Pfizer in Ann Arbor, Michigan, where she rose to the upper echelon of Discovery Senior Leadership team, being among the top 10% of the Discovery organization. Under the co-leadership of Dr. Augelli-Szafran, Development Candidates from two drug discovery projects were identified: PD 0202091 and PD 0118057, amyloid aggregation inhibitors for the treatment of Alzheimer’s disease and PD 0287383 and PD 0610002, mGluR5 antagonists for the treatment of anxiety and osteoarthritis. Other highlights of her contributions were research efforts towards clinical candidate CI-988, a Cholecystokinin (CCK) antagonist for the treatment of anxiety, clinical candidate CI-1017, an m1 muscarinic agonist for treatment of dementia and then co-leadership of an m4 muscarinic project that led to the identification PD 0102807, the most potent and selective synthetic m4 muscarinic antagonist known for the treatment of Parkinson’s disease. Currently, Dr. Augelli-Szafran’s early efforts at LEAD have generated several compounds within a few different chemical series that retain selective inhibition of Aβ production in γ-secretase assays that modulate substrate selectivity by inhibiting Aβ production, but not affecting Notch processing. Dr. Augelli-Szafran’s scientific record includes more than 100 publications and presentations and 18 patents.
Michael S. Wolfe, Ph.D., Founder and Advisor of LEAD
Michael S. Wolfe, Ph.D. is Associate Professor of Neurology at Harvard Medical School and Brigham and Women’s Hospital. Dr. Wolfe seeks to understand the basic biochemistry underlying Alzheimer’s disease and to identify therapeutic strategies. Of particular interest to the Wolfe lab is the mechanism of production of amyloid ß-protein (Aß), which deposits progressively with age in areas of the brain important for memory and cognition. In 1998, Dr. Wolfe published the first designed inhibitor of γ-secretase, an enzyme that performs the final step in the production of Aß. In 1999, he and Dr. Selkoe discovered the identity of γ-secretase as the protein, presenilin, which also causes the most aggressive form of familial AD. For his achievements in medicinal chemistry and biology, Dr. Wolfe received the Sato Memorial International Award from the Pharmaceutical Society of Japan.
Dennis J. Selkoe, M.D., Founder and Advisor of LEAD
Dennis J. Selkoe, M.D., the Vincent and Stella Coates Professor of Neurologic Diseases at Harvard Medical School and Brigham and Women’s Hospital, has devoted his career to the study of Alzheimer’s disease and related basic biological questions. Dr. Selkoe originally developed a method for isolating the neurofibrillary tangles that are a hallmark of AD and helped discover their subunit protein, tau. Subsequently, he has conducted extensive experiments on amyloid ß-protein (Aβ) and its precursor. He discovered that Aβ is produced normally by brain cells throughout life and helped formulate the “amyloid hypothesis”, now recognized as the leading theory of Alzheimer causation. These and other advances have led to Dr. Selkoe’s receipt of the Potamkin Prize, the Metropolitan Life Foundation Award and the A.H. Heineken Prize for Medicine.
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Han-Xun Wei, Ph.D., Senior Chemist
Han-Xun Wei, Ph.D. received his Ph.D. degree (1995) in Organic Chemistry from Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai, China. He then spent 1½years with Professor Lin Guo Qiang at Shanghai Institute of Organic Chemistry as a Postdoctoral Fellow where he synthesized chiral transition metal complexes. Dr. Wei then went on to Texas Tech University where he first spent 3 years as a Postdoctoral Fellow doing synthetic methodology and developing new asymmetric reactions. He remained at Texas Tech University for two more years as a Senior Research Fellow working on the total synthesis of Volicitin. In 2004, Dr. Wei joined Boehringer Ingelheim Pharmaceuticals, Inc. as a senior research scientist in the Department of Process and Development. Here he spent one year doing a multi-gram synthesis of BI207127 before moving to Professor E. J. Corey’s lab at Harvard University as Postdoctoral Research Fellow. His time spent in Professor Corey’s laboratory was focused on further development of an enantioselective Ireland-Claisen rearrangement. After 1½years in Professor Corey’s laboratory, Dr. Wei joined LEAD at Brigham and Women’s Hospital and Harvard Medical School. His research interests include catalytic asymmetric synthesis and the development of practical processes for the synthesis of new biologically active compounds. He is the author of more than 70 papers and abstracts.
Dai Lu, Ph.D., Senior Chemist
Dr. Dai Lu received his B.S. degree in Organic Chemistry from Nankai University (1987), and his M.S. degree in Medicinal Chemistry from Peking Union Medical College (1991). His Ph.D. degree in Medicinal Chemistry was obtained from the University of Connecticut (2005), followed by NIH postdoctoral training at the Center for Drug Discovery of Northeastern University in Boston, Massachusetts. From 1991 to1994, Dr. Dai Lu was a research scientist at the Institute of Materia Medica, Chinese Academy of Medical Sciences, Shanghai, China, where he was involved in the research of antitumoral drugs, Heinanensine and Taxol, and the anti-anxiety drug, Agarofuran. From 1992-1994, he was a member of the scientific board of Bellona Pharmaceuticals, Inc., and a key scientist for the development of Gadopentetate dimeglumine, the first MRI enhancing agent in China. From 1995-2004, Dr. Dai Lu was involved in the synthesis of cannabinergic molecules as agents for immune-modulatory and analgesic drugs at the School of Pharmacy, University of Connecticut. In 1996, he discovered the first selective ligand for the peripheral cannabinoid receptor., followed by the discovery of the the first class of intrinsically fluorescent ligands for the cannabinoid receptors in 1999 and the first water-soluble cannabinoid in 2001. Dr. Dai Lu has received several awards for his research accomplishments, including Boehringer Ingelheim Fellowship (1998-2000), Richardson-Vicks/A. Francis Summa Memorial Award (2003), and the Travel Award from International Cannabinoid Research Society (2003, 2004). Dr. Dai Lu’s scientific record in medicinal chemistry includes more than 25 publicationspresentations and 7 patents.
Jing Zhang, M.S., Research Specialist
Jing Zhang received her B.S. degree in 1997 from Sichuan University, China.
She then joined Sichuan Industrial Institute of Antibiotics as a research scientist where she was involved in the development of control standards for new drugs. She obtained her M.S. degree in pharmaceutical science in 2006 from the University of Connecticut where she worked as a research assistant at the Center for Drug Discovery. Her focus of research was in the synthesis of cannabimimetics as potential drug candidates that targeted the endocannabinoid system. Jing then joined LEAD in July 2006 as a Research Specialist. Her current efforts are towards the synthesis of potential therapeutics for the treatment of Alzheimer’s disease.
Yongli Gu, M.S., Research Specialist
Yongli Gu received her B.S. degree in 1998 in Biochemistry from East China Normal University, Shanghai, China. She then went on to receive her M.S. degree in Biochemistry at Kansas State University in 2003. She then spent one year as a research assistant at Kansas State University where she investigated the function of a new protein in a pea aphid and looked at various gene expressions in zebrafish. Ms. Gu then moved to Boston College and worked as a research associate
mainly studying the histone modifications and chromatin assembly. Yongli then joined LEAD in July 2006 as a Research Specialist. Her main efforts currently involve isolation and purification of the gamma-secretase protein as well as in vitro testing of potential inhibitory molecules targeted therapeutics for the treatment of Alzheimer’s disease.
Vivien Sun
Vivien Sun is a fourth year undergraduate student at Harvard University, majoring in Chemistry and Chemical Biology. Vivien’s involvement in LEAD consists of the synthesis of γ-secretase modulators. Vivien’s interests include the biochemistry of neurodegenerative diseases, as well as organic synthesis and the drug discovery process.
Abigail Harpstead
Abigail Harpstead is a third year undergraduate student at Harvard University majoring in Biochemistry with a citation in Spanish. Ms. Harpstead’s involvement in LEAD consists of understanding the biochemistry of gamma-secretase and then studying the effect of small molecule inhibitors or modulators on this secretase. Ms. Harpstead is also interested in becoming familiar with the drug discovery process towards a treatment for Alzheimer’s disease.
Catharine Makinster
Catharine Makinster provides administrative support to LEAD. Ms. Makinster previously worked as a software developer and trainer for International Aero Engines in East Hartford, CT. Ms. Makinster received her B.S. degree in Speech and Hearing Science from the University of Iowa.
Interim members:
Pamela Osenkowski, Ph.D. Postdoctoral Fellow
Dr. Pamela Osenkowski, a Postdoctoral Fellow in Drs. Wolfe and Selkoe’s laboratories, participated in the LEAD drug discovery effort by screening LEAD compounds in an in vitro assay using purified γ-secretase. Dr. Osenkowski obtained her Ph.D. in Cancer Biology from Wayne State University in Detroit, Michigan, where she studied the cell surface regulation of membrane-type 1-matrix metalloproteinase in cancer progression. Her current research interests include the substrate selectivity and regulation of γ-secretase by small molecules.
Wenjuan Ye, B.S., Research Technican
Wenjuan Ye, a Research Technician in Dr. Selkoe’s laboratory, workson the Presenilin project, and participated in the LEAD drug discovery effort by screening LEAD compounds in an in vitro assay using purified γ-secretase. She received her medical degree from the First Medical School of Shanghai, China and obtained her Certificate of Laboratory Technical Skills from the School of Medicine, Boston University. From 1994-2000, Wenjuan worked as a Laboratory Associate in Dr. Eric Landerat’s group at the Whitehead Institute/MIT Genome Center and participated in the human genome project. Her research interest is in the substrate selectivity and regulation of γ-secretase by small molecules.
LEAD Collaborators:
Laboratory for Drug Discovery in Neurodegeneration (LDDN): LDDN is dedicated to advancing hits identified from high-throughput compound screens relevant to neurological diseases such as Parkinson’s and ALS as well as Alzheimer’s disease. http://www.neurodiscovery.harvard.edu/research-collaborations/lddn.html
Weiming Xia, Ph.D. and laboratory
xialab.bwh.harvard.edu
