Andrew Stern, PhD

Director of Novel Therapeutics, Drug Discovery Institute, Associate Professor of Computational and Systems Biology

Andrew Stern, PhD

Sternam@pitt.edu

Office: W957 BST
Phone: 412-648-9897
Fax:

Department of Computational and Systems Biology

Biosketch

State University of New York at Stony Brook B.S. Chemistry 1971
University of California at Los Angeles Ph.D Biological Chemistry 1977
Brandeis University Postdoctoral Fellow Biochemistry 1980

I joined the Drug Discovery Institute of University of Pittsburgh School of Medicine as the Director of Novel Therapeutics in September, 2012. My goal is to provide team-oriented therapeutics-focused scientific leadership to help guide highly collaborative multidisciplinary drug and biomarker discovery teams comprised of experienced professionals, fellows and graduate students. I have experience leading drug discovery teams in both the academic and industrial communities from an early discovery stage through clinical development and approval. Prior to joining the University of Pittsburgh, I served as the Associate Director, Novel Therapeutics at the Broad Institute of Harvard and MIT. I co-led 5 cancer-related projects (please see corresponding publications below) and was responsible for designing and implementing several phenotypic screens and animal model studies in conjunction with integrative approaches to target identification. As one example we demonstrated that AURKA kinase was an essential negative regulator of polyploidization in acute megakaryocytic leukemia and through a novel target identification approach have been able to repurpose a clinical candidate for this specific indication. This study inspired the development of the Quantitative Systems Pharmacology approach used in the current proposal. As another example, we developed an extensive pharmacogenomic database involving the Cancer Cell Line Encyclopedia (CCLE) with potential impact for patient stratification that associated activating mutations in beta catenin with sensitivity to navitoclax, a BCL2 family antagonist. In addition I co-led the effort to establish the Broad Institute as a MLPCN Core Screening Center. Before joining the Broad, I spent 17 years in the pharmaceutical industry with Merck and then DuPont/Merck Pharmaceuticals where I served as the Executive Director, Chemical Enzymology. In addition to playing a key role in the discovery, development, and approval of the nonnucleoside reverse transcriptase inhibitor for HIV, Sustiva, my team identified presenilin as the pharmacologic target of gamma-secretase inhibitors that led to clinical candidates for Alzheimer’s disease and oncology indication. In addition to experience developing drugs, I led the effort at Merck/DuPont that elucidated the mechanism of drug- induced thrombocytopenia by a class of fibrinogen receptor antagonists. Based upon these studies, we then developed a diagnostic test for predicting those individual patients at risk for developing thrombocytopenia thereby reducing the incidence from 2-5% to <0.1%. My 25 years of experience in drug and biomarker discovery and development, target identification, and physiologically relevant assay design will enable me to help our highly collaborative multidisciplinary team elucidate the mechanisms underlying tumorigenesis, metastasis, and resistance to therapy by identifying small molecules probes with the ultimate goal of developing novel therapies and biomarkers. My research team has collaborated and published together with the Oesterreich laboratory preclinical and clinical studies characterizing those ESR1 mutations acquired during estrogen deprivation therapy.

  1. A Perspective on Implementing a Quantitative Systems Pharmacology Platform for Drug Discovery and the Advancement of Personalized Medicine. Stern AM, Schurdak ME, Bahar I, Berg JM, Taylor DL. Journal of biomolecular screening. 2016; 21(6):521-34. NIHMSID: NIHMS771367 PubMed [journal]PMID: 26962875 PMCID: PMC4917453
  2. Sensitive Detection of Mono- and Polyclonal ESR1 Mutations in Primary Tumors, Metastatic Lesions, and Cell-Free DNA of Breast Cancer Patients. Wang P, Bahreini A, Gyanchandani R, Lucas PC, Hartmaier RJ, Watters RJ, Jonnalagadda AR, Trejo Bittar HE, Berg A, Hamilton RL, Kurland BF, Weiss KR, Mathew A, Leone JP, Davidson NE, Nikiforova MN, Brufsky AM, Ambros TF, Stern AM, Puhalla SL, Lee AV, Oesterreich S. Clinical cancer research : an official journal of the American Association for Cancer Research. 2016; 22(5):1130-7. NIHMSID: NIHMS733596 PubMed [journal]PMID: 26500237 PMCID: PMC4775406
  3. Treating gynecologic malignancies with selective estrogen receptor downregulators (SERDs): promise and challenges. Boisen MM, Andersen CL, Sreekumar S, Stern AM, Oesterreich S. Molecular and cellular endocrinology. 2015; 418 Pt 3:322-33. PubMed [journal]PMID: 26276546
  4. Niche-Based Screening in Multiple Myeloma Identifies a Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors. Chattopadhyay S, Stewart AL, Mukherjee S, Huang C, Hartwell KA, Miller PG, Subramanian R, Carmody LC, Yusuf RZ, Sykes DB, Paulk J, Vetere A, Vallet S, Santo L, Cirstea DD, Hideshima T, Dančík V, Majireck MM, Hussain MM, Singh S, Quiroz R, Iaconelli J, Karmacharya R, Tolliday NJ, Clemons PA, Moore MA, Stern AM, Shamji AF, Ebert BL, Golub TR, Raje NS, Scadden DT, Schreiber SL. Cell reports. 2015; NIHMSID: NIHMS655802 PubMed [journal]PMID: 25660025 PMCID: PMC4524791
  5. A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities. Joy ME, Vollmer LL, Hulkower K, Stern AM, Peterson CK, Boltz RC, Roy P, Vogt A. PloS one. 2014; 9(2):e88350. PubMed [journal]PMID: 24520372 PMCID: PMC3919756