Biography

Dr. Wenliang Li’s research is to study novel molecular mechanisms of cancer metastasis with the goal of identifying new biomarkers and drug targets for the development of better therapeutics for human cancers.

Dr. Li obtained his Ph.D. in Genetics from Case Western Reserve University in 2004. His dissertation work was conducted in Dr. Bryan Williams’ lab at Cleveland Clinic Foundation, where he constructed a large cancer-specific cDNA microarray and used it to identify gene expression patterns that were associated with genetics and prognosis of human Wilms tumors. He then joined Dr. Ed Harlow’s lab at Harvard Medical School for his postdoctoral training, where he provided critical contributions in a series of collaborative studies in identifying kinases controlling survival and proliferation of human normal and tumor cells. In 12/2010, Dr. Li joined the Brown Foundation Institute of Molecular Medicine, UTHSC-Houston.

Cancer metastasis, the spread of tumor to other parts of patient’s body, is responsible for over 90% of cancer death. However, it is still poorly understood and the current approaches to prevent or treat human metastatic diseases are largely unsuccessful. Through genomics, RNAi and cDNA functional screens, Dr. Li’s lab has identified several critical but previously unknown regulators for cancer metastasis. Signaling pathways and molecular mechanisms of these genes are in study with molecular, cellular, biochemical, genomic and proteomic approaches, genetic and xenograft mouse models, as well as cancer patient samples.

For example, Dr. Li’s lab is studying GRK3 (G protein-coupled receptor kinase 3), a kinase they identified from shRNA/cDNA screening, in the progression of CRPC (castration resistant prostate cancer), especially the highly metastatic variant of CRPC, the t-NEPC (treatment-related neuroendocrine prostate cancer). Specific inhibitors targeting some of these novel regulators have been or are being identified from molecular docking analyses (virtual screening with computer) or compound library screening on bench.

One group of exciting new cancer targets actively pursued in Dr. Li lab are cell surface or secreted proteins. Their roles and mechanisms in cancer progression are being investigated. Through collaborations with neighboring lab of Drs. Ningyan Zhang and Zhiqiang An, Director of Texas Therapeutics Institute, Dr. Li lab is discovering and characterizing novel antibodies as therapeutics candidates. Some of them will be further developed into other antibody-based therapies, such as antibody-drug conjugates (ADC), bio-specific antibody or CART cell therapy.

Another exciting research program in Dr. Li’s lab is involved in identifying and studying novel regulators of epithelial-mesenchymal transition (EMT). EMT, a developmental process, is believed to play a key role in drug resistance, organ fibrosis and cancer metastasis. Dr. Li’s lab was the first group to perform a kinome cDNA screening on EMT and has identified several new critical regulators of EMT. Investigations of the molecular mechanisms of these kinases have had a significant impact in expanding our knowledge in cancer progressing. Some of these kinases are being targeted by novel inhibitors.

Awards:

  1. American Cancer Society Cancer Research Scholar, 2017
  2. Rising STARS Award, University of Texas System, 2010
  3. AACR-Aflac Scholar-In-Training Award, 2009
  4. Excellence in Graduate Research Award, Cleveland Clinic Foundation, 2004

Areas of Interest

Research Interests

  • Biology and targeting of neuroendocrine prostate cancer and small cell lung cancer.
  • Novel therapeutic antibodies targeting critical surface or secreted cancer regulators.
  • Combinations of our novel therapeutics with anti-PD1/PD-L1 antibodies to improve immunotherapy in prostate and lung cancers.
  • Lineage plasticity and acquired resistance to cancer therapeutics.
  • Mechanisms of novel cancer metastasis regulators identified from shRNA/cDNA screening.
  • New pathways and mechanisms of epithelial-mesenchymal transition.

Publications

Selected Publications

  1. Zheng D, Zhang Y, Yang S, Su N, Bakhoum M, Zhang Z, Naderinezhad S, Mao Z, Wang Z, Zhou T, Li W*. Androgen deprivation induces neuroendocrine phenotypes in prostate cancer cells through CREB/EZH2-mediated downregulation of REST. Cell Death Discovery 2024 May 22;10(1):246. doi: 10.1038/s41420-024-02031-1.
  2. Naderinezhad S, Zhang G, Wang Z, Zheng D, Hulsurkar M, Su N, Han Y, Shen T, Li W*. A novel GRK3-HDAC2 regulatory pathway is a key direct link between neuroendocrine differentiation and angiogenesis in prostate cancer progression. Cancer Letters 2023 Aug 4;571:216333. doi: 10.1016/j.canlet.2023.216333.
  3. Liu J, Chiang HC, Xiong W, Laurent V, Griffiths SC, Dülfer J, Deng H, Sun X, Yin YW, Li W, Audoly LP, An Z, Schürpf T, Li R, Zhang N. A highly selective humanized DDR1 mAb reverses immune exclusion by disrupting collagen fiber alignment in breast cancer. J Immunother Cancer. 2023 Jun;11(6): e006720. doi: 10.1136/jitc-2023-006720.
  4. Li Y, Fan Y, Xu J, Huo L, Scott AW, Jin J, Yang B, Shao S, Ma L, Wang Y, Yao X, Pizzi MP, Da Silva MS, Zhang G, Zhuo L, Cho EJ, Dalby KN, Shanbhag ND, Wang Z*, Li W*, Song S*, Ajani JA*. GRK3 is a poor prognosticator and serves as a therapeutic target in advanced gastric adenocarcinoma. J Exp Clin Cancer Res (2022) 41:257-275. https://doi.org/10.1186/s13046-022-02463-6.
  5. Wang Z, Hulsurkar M, Zhuo L, Xu J, Yang H, Naderinezhad S, Wang L, Zhang G, Ai N, Li L, Chang JT, Zhang S, Fazli L, Creighton CJ, Bai F, Ittmann MM, Gleave GE, Li W*. CKB inhibits epithelial-mesenchymal transition and prostate cancer progression by sequestering and inhibiting AKT activation. Neoplasia 2021 Oct 23;23(11):1147-1165.
  6. Wang Z, Zhao Y, An Z, Li W*. Molecular links between neuroendocrine differentiation and angiogenesis in prostate cancer progression. Frontiers in Oncology, 2020 Jan 21;9:1491 (Invited Review).
  7. Lee DK, Liu Y, Liao L, Li W, Danielpour D, Xu J. Neuroendocrine prostate carcinoma cells originate from the p63-expressing basal cells but not the pre-existing adenocarcinoma cells in mice. Cell Research. 2019 May;29(5):420-422
  8. Chi S, Liu Y, Zhou X, Feng D, Xiao X, Li W, Zhao Y, Wang H. Knockdown of long non-coding HOTAIR enhances the sensitivity to progesterone in endometrial cancer by epigenetic regulation of progesterone receptor isoform B. Cancer Chemotherapy and Pharmacology. 2019 Feb;83(2):277-287.
  9. Zhang Y, Zheng D, Zhou T, Song H, Hulsurkar M, Su N, Liu Y, Wang Z, Shao L, Ittmann M, Gleave M, Xu F, Liao W, Wang H, Li W*. Androgen deprivation promotes neuroendocrine differentiation and angiogenesis through CREB-EZH2-TSP1 pathway in prostate cancers. Nature Communications, 2018 Oct 4; 9(1):4080.
  10. Zhao Y, Li W*. Beta-adrenergic signaling on neuroendocrine differentiation, angiogenesis, and metastasis in prostate cancer progression. Asian Journal of Andrology 2018 May 29 (Invited Review).
  11. Hulsurkar M, Li Z, Li X, Zhang Y, Zheng D, Li W*. Beta-adrenergic signaling promotes tumor angiogenesis and prostate cancer progression through HDAC2-mediated suppression of thrombospondin-1. Oncogene 2016, September 19.
  12. Sang M, Hulsurkar M, Zhang X, Song H, Zheng D, Zhang Y, Li M, Zhang S, Xu J,  Ittmann M, Li W*. GRK3 is a direct target of CREB activation and regulates neuroendocrine differentiation of prostate cancer cells. Oncotarget 2016, May 14.
  13. Li L, Li W*. Epithelial-mesenchymal transition in human cancer: comprehensive   reprogramming of metabolism, epigenetics and differentiation. Pharmacology & Therapeutics 2015 Jun;150:33-46 (Invited Review).
  14. Li L, Liu C, Amato RJ, Chang JT, Du G, Li W*. CDKL2 promotes epithelial- mesenchymal transition and breast cancer progression. Oncotarget 2014 Nov;15;5(21):10840-53.
  15. Li W*, Ai N,  Wang S, Bhattacharya N, Vrbanac V, Collins M, Signoretti S, Hu Y, Boyce FM, Gravdal K, Halvorsen OJ, Nalwoga H, Akslen LA, Harlow E*, Watnick  RS. GRK3 is essential for metastatic cells and promotes prostate tumor progression. Proceedings of the National Academy of Sciences USA (PNAS) 2014 Jan 28;111(4):1521-6.
  16. Baldwin A, Grueneberg DA, Hellner K, Sawyer J, Grace M, Li W, Harlow E,  Münger K. V. Synthetic lethal interactions between p53 and the protein kinases SGK2 and PAK3. Proceedings of the National Academy of Sciences USA (PNAS). 2010 Jul 13;107(28):12463-8.
  17. Grueneberg DA$, Li W$, Davies JE and Harlow, E. IV. shRNA screens identify  kinase requirements in human cells: differential kinase requirements in cervical   and renal human tumor cell lines. Proceedings of the National Academy of   Sciences USA (PNAS). 2008 Oct 28;105(43):16490-5. $co-first author
  18. Bommi-Reddy A, Almeciga I, Sawyer J, Geisen C, Li W, Harlow E, Kaelin WG Jr, Grueneberg DA. III. Altered Kinase Requirements in VHL-/- Renal Carcinoma Cells Detected in a Pilot Synthetic Lethal Screen. Proceedings of the National Academy of    Sciences USA (PNAS). 2008 Oct 28;105(43):16484-9.
  19. Baldwin A, Li W, Grace M, Harlow E, Münger K and Grueneberg DA. II. Genetic Interaction Screens Identify Alterations in Kinase Requirements Following HPV16 E7 Expression in Cancer Cells. Proceedings of the National Academy of Sciences USA (PNAS). 2008 Oct 28;105(43):16478-83.
  20. Grueneberg DA$, Degot S$, Pearlberg J$, Li W$, Davies JE$, Baldwin A$,  Endege W, Doench J, Sawyer J, Hu Y, Boyce F, Xian J, Munger K, Harlow E. I.  Comparing Kinase requirements across Various Cell types. Proceedings of the National Academy of Sciences USA (PNAS). 2008 Oct 28;105(43):16472-7. $co-first author. Note: The 4 PNAS papers in 2008 were selected as one of Signaling Breakthroughs of 2008 by the annual Editorial Guide of Science Signaling.
  21. Sengupta S, Kim KS, Berk MP, Escobar P, Li W, Lindner DJ, Williams BRG, Xu Y. Lysophosphatidic acid down regulates tissue inhibitor of metalloproteinases (TIMPs), which are negatively involved in LPA-induced cell invasion. Oncogene. 2007 May 3;26(20):2894-901.
  22. Pearlberg J, Degot S, Endege W, Park J, Davies J, Gelfand E, Sawyer J, Conery A, Doench J, Li W, Gonzalez L, Boyce FM, Brizuela L, Labaer J, Grueneberg D, Harlow E. Screens using RNAi and cDNA expression as surrogates for genetics in mammalian tissue culture cells. Cold Spring Harb Symp Quant Biol. 2005;70:449-59.
  23. Li W, Kessler P, Yeger H, Alami J, Reeve AE, Heathcott R, Skeen J, Williams BRG. A gene expression signature for relapse in primary Wilms tumor. Cancer Research. 2005 Apr 1; 65(7):2592-601.
  24. Li W, Kessler P, Williams BRG. Transcript profiling of Wilms tumors reveals systematic connections to kidney morphogenesis and a gene expression pattern associated with unfavorable histology. Oncogene. 2005 Jan 13; 24(3):457-68.