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Jeffrey R. Peterson, PhD

About

Research Program

Rho GTPase effectors regulate the cellular actin cytoskeleton
Crystal structure of a chemical inhibitor bound to Pak5
A liquid-handling robot for high throughput screening assays

 

Education and Training

Educational Background

  • PhD, Cell Biology, Yale University, New Haven, CT, 1997
  • BA, Biology, Swarthmore College, Swarthmore, PA, 1991

Memberships

  • American Association for Cancer Research
  • American Society for Cell Biology

Honors & Awards

  • American Cancer Society Research Scholar, 2008
  • American Association for Cancer Research Career Development Award, 2006
  • NIH Postdoctoral Fellow, 1998-2001
  • John Enders Grantee, Yale University, 1997
  • Fulbright Fellow, University of Heidelberg, Germany, 1991-1992
  • Merck Corporation Research Fellow, 1990
Research Profile

Research Program

Research Interests

Cancer Signaling and Metabolism

  • Identifying and targeting metabolic weakness of triple negative breast cancer
  • Understanding how cancer cell signaling impacts cell metabolism
  • Controlling abberant cancer signaling and metabolism through the development and characterization of new drug-like small molecules

Lab Overview

Peterson Lab

We seek to understand how cell signaling and metabolism are altered in cancer and to use that information to devise new therapeutic strategies. We use whatever approaches are required, whether protein biochemistry, high throughput screening, or genetics in model organisms, to advance our quest.

  1. Targeting molecular alterations that drive triple negative breast cancer growth
    TNBC is a poorly understood but malignant type of breast cancer that disproportionately affects younger women and African-American women.  There are currently no targeted therapies for TNBC but they are desperately needed. We have been characterizing molecular alterations in cell signaling and metabolic pathways that contribute to TNBC cell growth. We utilize cell line models and human tumor xenografts as model systems to developing new therapeutic approaches for this malignant breast cancer subtype. Our recent work has identified a metabolic weakness of TNBC and we are currently testing whether existing drugs that alter this pathway are active against this disease in cell line and xenograft models.  In addition, we screen small molecule libraries to identify new lead compounds targeting vulnerable pathways in breast cancer.

  2. How do signaling pathways that drive cancer cell growth alter cellular metabolism to support tumor growth?
    We have identified a novel link between growth factor signaling and nucleotide biosynthesis.  Proliferating cells such as cancer cells have an elevated requirement for nucleotides.  Rate-limited enzymes in nucleotide biosynthesis, IMPDH and CTPS, can reversibly polymerize under conditions of nucleotide deficit.  We hypothesize that this assembly enhances nucleotide biosynthesis in an attempt to restore nucleotide levels and may be relevant in supporting the growth of cancer cells.  Importantly, we have identified a kinase as a regulator of the polymerization of these enzymes. Furthermore we have identified novel inhibitors of this kinase that might represent a way to starve cancer cells of nucleotides and halt their growth. We are working at all levels; from studying the biochemistry of purified proteins to their function in genetically engineered organisms to address these fundamental questions:

    1. In what biological contexts is polymerization of IMPDH and CTPS important?

    2. How is their assembly regulated?

    3. What other components co-assemble with IMPDH and CTPS?

    4. How does assembly affect their catalytic activity?

The answers to these questions will reveal how cellular signaling pathways can influence cell metabolism and may suggest new therapeutic approaches in cancer.

Lab Staff

Alexander Beatty, PhD

Postdoctoral Fellow

Room: P3165
215-728-3652

Tanu Singh

Scientific Associate

Room: P3165
215-728-3652
Publications

Selected Publications

Simonet JC, Foster MJ, Lynch EM, Kollman JM, Nicholas E, O'Reilly AM, Peterson JR. CTP synthase polymerization in germline cells of the developing Drosophila egg supports egg production. Biol Open. 2020 9(7).

Simonet JC, Burrell AL, Kollman JM, Peterson JR. Freedom of assembly: metabolic enzymes come together. Mol Biol Cell. 2020 31(12):1201-1205.

Kiseleva AA, Korobeynikov VA, Nikonova AS, Zhang P, Makhov P, Deneka AY, Einarson MB, Serebriiskii IG, Liu H, Peterson JR, Golemis EA. Unexpected Activities in Regulating Ciliation Contribute to Off-target Effects of Targeted Drugs. Clin Cancer Res. 2019 25(13):4179-4193.

Beatty A, Singh T, Tyurina YY, Nicolas E, Maslar K, Zhou Y, Cai KQ, Tan Y, Doll S, Conrad M, Bayır H, Kagan VE, Rennefahrt U, Peterson JR. Conjugated linolenic fatty acids trigger ferroptosis in triple-negative breast cancer. [preprint]. 2019.

Duong-Ly KC, Kuo YM, Johnson MC, Cote JM, Kollman JM, Soboloff J, Rall GF, Andrews AJ, Peterson JR. T cell activation triggers reversible inosine-5'-monophosphate dehydrogenase assembly. J Cell Sci. 2018 131(17).

Beatty A, Fink LS, Singh T, Strigun A, Peter E, Ferrer CM, Nicolas E, Cai KQ, Moran TP, Reginato MJ, Rennefahrt U, Peterson JR. Metabolite Profiling Reveals the Glutathione Biosynthetic Pathway as a Therapeutic Target in Triple-Negative Breast Cancer. Mol Cancer Ther. 2018 (1):264-275.

Anthony SA, Burrell AL, Johnson MC, Duong-Ly KC, Kuo YM, Simonet JC, Michener P, Andrews A, Kollman JM, Peterson JR. Reconstituted IMPDH polymers accommodate both catalytically active and inactive conformations. Mol Biol Cell. 2017 28(20):2600-2608.

Kurimchak AM, Shelton C, Duncan KE, Johnson KJ, Brown J, O'Brien S, Gabbasov R, Fink LS, Li Y, Lounsbury N, Abou-Gharbia M, Childers WE, Connolly DC, Chernoff J, Peterson JR, Duncan JS. Resistance to BET Bromodomain Inhibitors Is Mediated by Kinome Reprogramming in Ovarian Cancer. Cell Rep. 2016 16(5):1273-1286.

Duong-Ly KC, Devarajan K, Liang S, Horiuchi KY, Wang Y, Ma H, Peterson JR. Kinase Inhibitor Profiling Reveals Unexpected Opportunities to Inhibit Disease-Associated Mutant Kinases. Cell Rep. 2016 14(4):772-781.

Xu Q, Malecka KL, Fink L, Jordan EJ, Duffy E, Kolander S, Peterson JR, Dunbrack RL Jr. Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases. Sci Signal. 2015 8(405):rs13.

Fink LS, Beatty A, Devarajan K, Peri S, Peterson JR. Pharmacological profiling of kinase dependency in cell lines across triple-negative breast cancer subtypes. Mol Cancer Ther. 2015 (1):298-306.

Additional Publications

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