David Goodrich

PhD

Special Interests:

Understanding molecular mechanisms underlying tumor suppression mediated by the RB1 and TP53 genes Identifying genes involved in prostate cancer metastasis Discerning how transcriptionally formed R-loops contribute to cancer initiation and progression Understanding molecular mechanisms underlying the non-genetic adaptations of cancer cells to selective pressures like metastasis and therapy Elucidating how tumor suppression genes control cancer lineage plasticity and acquired therapeutic resistance

About David Goodrich

Biography:

View the Goodrich Lab

Positions

Roswell Park Comprehensive Cancer Center

  • Distinguished Professor of Oncology
  • Member, Molecular Pharmacology and Cancer Therapeutics Graduate Program
  • Associate Dean for Postdoctoral Education
  • Department of Pharmacology & Therapeutics

Background

Education and Training:

  • 1989 - PhD - Molecular Biology, University of California, Berkeley, CA
  • BS, Molecular Biology, University of Wisconsin, Madison, WI

Honors & Awards:

  • RPMI Award
  • Dean’s Award for Excellence in Graduate Education
  • Wilson Scholar
  • Leukemia Society Fellow
  • Giannini Medical Research Fellow
  • NRSA Predoctoral Fellow
  • Phi Beta Kappa
  • Knapp Research Fellow
  • Ingersol Prize in Physics

Research

Research Overview:

The long-term goals of my laboratory are to understand how genetic alterations in tumor suppressor genes drive cancer initiation, progression, and therapeutic resistance. The tumor suppressor genes we study are some of the most frequently altered genes in human cancer. Understanding how these genes function will refine our fundamental understanding of cancer and suggest novel therapeutic approaches to treat it. Our primary experimental approaches involve creation of genetically engineered mouse strains and patient derived organoids. Characterizing the effects of engineered genetic alterations helps us elucidate molecular mechanisms underlying cancer phenotypes of interest.

Our current primary focus is on cancer lineage plasticity, a phenomenon whereby cancer cells reprogram themselves to an alternative lineage or phenotypic state in order to adapt to selective pressures. We are finding that mutations in key tumor suppressor genes can increase cancer lineage plasticity, endowing these cancers with increased ability to metastasize and evade therapy.

We study prostate and lung cancer primarily, two important cancers where lineage plasticity has been documented to promote resistance to molecularly targeted therapies. Our goal is to discover underlying molecular mechanisms and leverage these mechanisms to devise novel therapeutic approaches. For example, we are testing whether targeting epigenetic regulatory factors or lineage specifying transcription factors can suppress cancer lineage plasticity and improve therapeutic outcomes using both mouse models and human clinical trials.

Meenalakshmi Chinnam
Mauricio Flores
Jena Hazen
Neha Jaiswal
Yanqing Wang
Xiaojing Zhang

Goodrich Lab


Publications

Full Publications list on PubMed

Chan JM, Zaidi S, Love JR, Zhao JL, Setty M, Wadosky KM, Gopalan A, Choo ZN, Persad S, Choi J, LaClair J, Lawrence KE, Chaudhary O, Xu T, Masilionis I, Linkov I, Wang S, Lee C, Barlas A, Morris MJ, Mazutis L, Chaligne R, Chen Y, Goodrich DW, Karthaus WR, Pe'er D, Sawyers CL. Lineage plasticity in prostate cancer depends on JAK/STAT inflammatory signaling. Science. 2022 Sep 9;377(6611):1180-1191. doi: 10.1126/science.abn0478. Epub 2022 Aug 18. PMID: 35981096.

Kumar R, Chaudhary AK, Woytash J, Inigo JR, Gokhale AA, Bshara W, Attwood K, Wang J, Spernyak JA, Rath E, Yadav N, Haller D, Goodrich DW, Tang DG, Chandra D. A mitochondrial unfolded protein response inhibitor suppresses prostate cancer growth in mice via HSP60. J Clin Invest. 2022 Jul 1;132(13):e149906. doi: 10.1172/JCI149906. PMID: 35653190; PMCID: PMC9246382.

Chinnam M, Xu C, Lama R, Zhang X, Cedeno CD, Wang Y, Stablewski AB, Goodrich DW, Wang X. MDM2 E3 ligase activity is essential for p53 regulation and cell cycle integrity. PLoS Genet. 2022 May 19;18(5):e1010171. doi: 10.1371/journal.pgen.1010171. Erratum in: PLoS Genet. 2022 Jun 27;18(6):e1010293. PMID: 35588102; PMCID: PMC9119546.

Flores M, Goodrich DW. Retinoblastoma Protein Paralogs and Tumor Suppression. Front Genet. 2022 Mar 18;13:818719. doi: 10.3389/fgene.2022.818719. PMID: 35368709; PMCID: PMC8971665.

Pearson JD, Huang K, Pacal M, McCurdy SR, Lu S, Aubry A, Yu T, Wadosky KM, Zhang L, Wang T, Gregorieff A, Ahmad M, Dimaras H, Langille E, Cole SPC, Monnier PP, Lok BH, Tsao MS, Akeno N, Schramek D, Wikenheiser-Brokamp KA, Knudsen ES, Witkiewicz AK, Wrana JL, Goodrich DW, Bremner R. Binary pan-cancer classes with distinct vulnerabilities defined by pro- or anti-cancer YAP/TEAD activity. Cancer Cell. 2021 Aug 9;39(8):1115-1134.e12. doi: 10.1016/j.ccell.2021.06.016. Epub 2021 Jul 21. PMID: 34270926.  

Park SH, Fong KW, Kim J, Wang F, Lu X, Lee Y, Brea LT, Wadosky K, Guo C, Abdulkadir SA, Crispino JD, Fang D, Ntziachristos P, Liu X, Li X, Wan Y, Goodrich DW, Zhao JC, Yu J. Posttranslational regulation of FOXA1 by Polycomb and BUB3/USP7 deubiquitin complex in prostate cancer. Sci Adv. 2021 Apr 7;7(15):eabe2261. doi: 10.1126/sciadv.abe2261. PMID: 33827814; PMCID: PMC8026124. 

Quaglia F, Krishn SR, Wang Y, Goodrich DW, McCue P, Kossenkov AV, Mandigo AC, Knudsen KE, Weinreb PH, Corey E, Kelly WK, Languino LR. Differential expression of αVβ3 and αVβ6 integrins in prostate cancer progression. PLoS One. 2021 Jan 22;16(1):e0244985. doi: 10.1371/journal.pone.0244985. PMID: 33481853; PMCID: PMC7822502. 

Shaurova T, Dy GK, Battaglia S, Hutson A, Zhang L, Zhang Y, Lovly CM, Seshadri M, Goodrich DW, Johnson CS, Hershberger PA. Vitamin D3 Metabolites Demonstrate Prognostic Value in EGFR-Mutant Lung Adenocarcinoma and Can be Deployed to Oppose Acquired Therapeutic Resistance. Cancers (Basel). 2020 Mar 13;12(3):675. doi: 10.3390/cancers12030675. PMID: 32183160; PMCID: PMC7140110. 

Knudsen ES, Nambiar R, Rosario SR, Smiraglia DJ, Goodrich DW, Witkiewicz AK. Pan-cancer molecular analysis of the RB tumor suppressor pathway. Commun Biol. 2020 Apr 2;3(1):158. doi: 10.1038/s42003-020-0873-9. PMID: 32242058; PMCID: PMC7118159. 

Knudsen ES, Pruitt SC, Hershberger PA, Witkiewicz AK, Goodrich DW. Cell Cycle and Beyond: Exploiting New RB1 Controlled Mechanisms for Cancer Therapy. Trends Cancer. 2019 May;5(5):308-324. doi: 10.1016/j.trecan.2019.03.005. Epub 2019 Apr 30. PMID: 31174843; PMCID: PMC6719339. 

Jin X, Ding D, Yan Y, Li H, Wang B, Ma L, Ye Z, Ma T, Wu Q, Rodrigues DN, Kohli M, Jimenez R, Wang L, Goodrich DW, de Bono J, Dong H, Wu H, Zhu R, Huang H. Phosphorylated RB Promotes Cancer Immunity by Inhibiting NF-κB Activation and PD-L1 Expression. Mol Cell. 2019 Jan 3;73(1):22-35.e6. doi: 10.1016/j.molcel.2018.10.034. Epub 2018 Dec 6. PMID: 30527665. 

Dick FA, Goodrich DW, Sage J, Dyson NJ. Non-canonical functions of the RB protein in cancer. Nat Rev Cancer. 2018 Jul;18(7):442-451. doi: 10.1038/s41568-018-0008-5. PMID: 29692417; PMCID: PMC6693677. 

Labbé DP, Sweeney CJ, Brown M, Galbo P, Rosario S, Wadosky KM, Ku SY, Sjöström M, Alshalalfa M, Erho N, Davicioni E, Karnes RJ, Schaeffer EM, Jenkins RB, Den RB, Ross AE, Bowden M, Huang Y, Gray KP, Feng FY, Spratt DE, Goodrich DW, Eng KH, Ellis L. TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup. Clin Cancer Res. 2017 Nov 15;23(22):7072-7083. doi: 10.1158/1078-0432.CCR-17-0413. Epub 2017 Sep 12. PMID: 28899973; PMCID: PMC5690819. 

Mu P, Zhang Z, Benelli M, Karthaus WR, Hoover E, Chen CC, Wongvipat J, Ku SY, Gao D, Cao Z, Shah N, Adams EJ, Abida W, Watson PA, Prandi D, Huang CH, de Stanchina E, Lowe SW, Ellis L, Beltran H, Rubin MA, Goodrich DW, Demichelis F, Sawyers CL. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science. 2017 Jan 6;355(6320):84-88. doi: 10.1126/science.aah4307. PMID: 28059768; PMCID: PMC5247742. 

Ku SY, Rosario S, Wang Y, Mu P, Seshadri M, Goodrich ZW, Goodrich MM, Labbé DP, Gomez EC, Wang J, Long HW, Xu B, Brown M, Loda M, Sawyers CL, Ellis L, Goodrich DW. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science. 2017 Jan 6;355(6320):78-83. doi: 10.1126/science.aah4199. PMID: 28059767; PMCID: PMC5367887.