Chair, Department of Biochemistry & Molecular Medicine
Ross Professor of Basic Science Research
Professor of Biochemistry and Molecular Medicine
Office Phone: 202-994-1439
Department: Biochemistry and Molecular Medicine
- BS Genetics, Fudan University, PRC, 1985
- PhD Molecular Biology, University of California, Berkeley, 1991
Dr. Rong Li has been working in gene regulation and breast cancer biology for more than two decades. He received his Ph.D. degree from the University of California at Berkeley in molecular biology of DNA replication and transcriptional regulation. As a postdoctoral fellow at the Cold Spring Harbor Laboratory, he expanded his research scope to include cell cycle regulation, DNA repair and DNA damage response. Since he became an independent investigator, first at the University of Virginia (1996-2006) and later at University of Texas Health Science Center at San Antonio (2007-2018), Dr. Li has led a productive research endeavor in several areas of breast cancer-related biomedical research. One major focus in his research is the role of the breast cancer susceptibility gene product BRCA1 in tissue-specific tumor suppression. Another research topic in his lab involves transcriptional regulation by RNA polymerase II-pausing factors during normal tissue homeostasis and pathogenesis. A third active research area in Dr. Li’s lab is the crosstalk among tumor, fat, and immune cells during cancer progression.
Dr. Li currently is chair of the Department of Biochemistry and Molecular Medicine, the George Washington University School of Medicine & Health Sciences. He is the Ross Professor of Basic Science Research. Dr. Li has published over 80 scientific papers, many in high-impact journals including Nature, Cell, Genes Dev, Cell Rep, Nat Commun, PNAS, and J Clin Invest. Dr. Li has served on several NIH study sections and currently is chair of the National Institutes of Health (NIH) Tumor Microenvironment (TME) study section. Dr. Li’s research has been continuously funded for more than two decades by NIH and other federal, state and private funding agencies.
Please visit the https://smhs.gwu.edu/li-lab/
Click https://smhs.gwu.edu/li-lab/publications to see Dr. Rong Li's published works.
Why do germ-line BRCA1 mutations predominantly affect breast and ovarian tissues in women?
Women who harbor cancer-predisposing germ-line mutations in BRCA1 have a significantly increased chance of developing breast and ovarian cancers. However, it is not clear whether the DNA repair activity of BRCA1 alone is sufficient to account for its sex- and tissue-specific tumor suppression function. We identified a BRCA1-binding protein COBRA1, which is identical to the B subunit of NELF (NELF-B) involved in pausing of RNA polymerase II (J Cell Biol 2001; Genes & Dev 2004). Using mouse genetics and clinical samples from BRCA1 mutation carriers, we recently discover a previously unrecognized, DNA repair-independent functional interaction between BRCA1 and COBRA1 in mammary gland development and tumor development (Nature Commun 2016; Nature Commun 2017). Our long-term objective in this project is to reconcile an enduring intellectual disconnect concerning BRCA1-associated cancer, thus catapulting understanding of BRCA1 cancer biology to a new level.
How can we rally antitumor activity of estrogen receptor beta?
ER-beta exhibits antitumor activity in multiple cancer types in both tumor-intrinsic and -extrinsic manners. However, little is known as to how such activity can be harnessed with high efficacy and precision. These major knowledge gaps hamper efforts to unleash ER-beta antitumor activity for cancer therapies. We recently discovered a phosphotyrosine-dependent signaling axis that controls ER-beta antitumor activity (J Clin Invest 2014; Oncotarget 2016). Furthermore, using preclinical models for multiple cancer types, we show that clinically safe small-molecule agents that elevate ER-beta signaling can significantly boost current anticancer therapies. Our ongoing study is aimed at rapidly translating our laboratory findings into clinical trials with the ultimate goal of helping improve clinical outcomes for larger numbers of cancer patients.
Crosstalk between adipocytes, immune cells and tumor cells in the breast tumor microenvironment
Adipose tissue plays an important role in breast cancer recurrence and mortality. In our published and unpublished work, we identified several previously unrecognized molecules in adipose tissue that regulate the crosstalk between tumor-stromal interactions in the breast tumor microenvironment. For example, we found a collagen receptor DDR1-initiated signaling cascade that transduces extracellular matrix signals and regulates the tumor-promoting endocrine output of adipose resident cells (Nature Commun 2014; J Biol Chem 2018). In a more recent study, we made the unexpected discovery that adipocytes express high levels of immune checkpoint protein PD-L1, which in turn modulates antitumor immunity and anti-PD-1/PD-L1 immunotherapies (Oncoimmunology, 2018). Our ultimate goal in this line of work is to enhance therapeutic efficacy of cancer treatment by targeting newly discovered signaling pathways involved in adipose-immune-tumor crosstalk.
Crosstalk between BRCA1 and Transcription in Breast Cancer
Regulation of Transcription Elongation in Adipose Homeostasis
Regulation of ER-beta Signaling in Carcinogenesis
1994-1997 Leukemia Society of America Special Fellow Award
1998-2000 March of Dimes, Basil O'Connor Award
2005 Academy of Distinguished Educators, Univ. Virginia School of Medicine
2009 President’s Council Excellence Award, Univ. Texas HSC San Antonio
2015-2018 Tom C. and Patricia H. Frost Endowed Chair
2019-present Ross Professor of Basic Science Research
Dr. Li has been actively involved in medical and graduate teaching over the past two decades. From 1999 to 2006, he taught carbohydrate and lipid metabolism, a significant section of the Human Biochemistry course for the first-year medical students (a typical class size of 130) at the School of Medicine, University of Virginia. In addition, Dr. Li taught various didactic courses for graduate students at University of Virginia and University of Texas Health Science Center at San Antonio. These include Molecular Genetics, Chromatin Structure, and Molecular Basis of Cancer. Dr. Li is involved in MS, PhD and MD education at the George Washington University. Dr. Li received the Basic Sciences Teaching Award in 1999 and was inducted into the Academy of Distinguished Educators in 2005, both at the University of Virginia School of Medicine.
- GW Cancer Center
Zhang X, Wang Y, Chiang H-C, Hsieh Y-P, Lu C, Park BH, Jatoi I, Jin VX*, Hu Y* and Li R*. (2019) BRCA1 mutations attenuate super-enhancer function and chromatin looping in haploinsufficient human breast epithelial cells. Breast Cancer Res. 21:51 (*co-corresponding authors)
Chiang H-C, Zhang X, Li J, Zhao X, Chen J, Wang HT-H, Jatoi I, Brenner A, Hu Y* and Li R*. (2019) BRCA1-Associated R-Loop Affects Transcription and Differentiation in Breast Luminal Epithelial Cells. Nucleic Acids Res. [Epub ahead of print] (*co-corresponding authors)
Wu B, Sun X, Gupta HB, Yuan B, Li J, Ge F, Chiang H-C, Zhang X, Zhang C, Zhang D, Yang J, Hu Y, Curiel TJ*, Li R*. (2018) Adipose PD-L1 Modulates PD-1/PD-L1 Checkpoint Blockade Immunotherapy Efficacy in Breast Cancer. Oncoimmunology. DOI: 10.1080/2162402X.2018.1500107 (*co-corresponding authors)
Zhang X*, Li R*. (2018) BRCA1-Dependent Transcriptional Regulation: Implication in Tissue-Specific Tumor Suppression. Cancers (Basel) 10:513 (*co-corresponding authors)
Zhang X, Chiang H-C, Wang Y, Zhang C, Smith S, Zhao X, Nair S, Michalek J, Jatoi J, Lautner M, Oliver B, Wang H, Petit A, Soler T, Brunet J, Mateo F, Pujana MA, Poggi E, Chaldekas K, Isaacs C, Peshkin BN, Ochoa O, Chedin F, Theoharis C, Sun L-Z, Curiel TJ, Elledge R, Jin VX*, Hu, Y*, Li R*. (2017) Attenuation of RNA Polymerase II Pausing Mitigates BRCA1-Associated R-loop Accumulation and Tumorigenesis. Nat Commun. 8:15908. (*co-corresponding authors)
Nair S, Zhang X, Chiang H-C, Jahid MJ, Wang Y, Garza P, April C, Salathia N, Banerjee T, Alenazi FS, Ruan J, Fan J-B, Parvin JD, Jin VX, Hu Y*, Li R*. (2016) Genetic Suppression Reveals DNA Repair-Independent Antagonism between BRCA1 and COBRA1 in Mammary Gland Development. Nat Commun. 7:10913. (*co-corresponding authors)
Clark CA, Gupta H, Sareddy GR, Pandeswara S, Lao S, Yuan B, Drerup JM, Padron A, Conejo-Garcia JR, Murthy K, Liu Y, Turk MJ, Thedieck K, Hurez V, Li R, Vadlamudi RK, Curiel TJ. (2016) Tumor-intrinsic PD-L1 signals regulate cell growth, pathogenesis and autophagy in ovarian cancer and melanoma. Cancer Res. 76:6964-6974.
Pan H, Qin K, Guo Z, Ma Y, April C, Gao X, Andrews TG, Bokov A, Zhang J, Chen Y, Weintraub ST, Fan J-B, Wang D, Hu Y, Aune GJ, Lindsey ML, Li R. (2014) Negative elongation factor controls energy homeostasis in cardiomyocytes. Cell Rep, 7:79. PMCID: PMC4277258.
Yuan B, Cheng L, Chiang H-C, Xu X, Han Y, Su H, Wang L, Zhang B, Li J, Tekmal J, Li X, Xie X, Wang T, Tekmal RR, Curiel TJ, Yuan Z-Y, Elledge R, Hu Y, Ye Q, Li R. (2014) A phosphotyrosine switch determines the antitumor activity of ERb. J. Clin. Invest. 124:3378. (highlighted in September 2014 issue of Cancer Discovery). PMCID: PMC4109526.
Ghosh S, Gu F, Wang CM, Lin CL, Liu J, Wang H, Ravdin P, Hu Y, Huang TH, Li R. (2014) Genome-wide DNA methylation profiling reveals parity-associated hypermethylation of FOXA1. Breast Cancer Res Treat. 147:653-9.
Ghosh S, Ashcraft K, Jahid MJ, April C, Ghajar CM, Ruan J, Wang H, Foster M, Hughes, DC, Ramirez, AG, Huang T, Fan JB, Hughes, D, Ramirez A, Hu Y, Li R. (2013) Regulation of adipose estrogen output by mechanical stress. Nat Commun. 4:1821. PMCID: PMC3921626.
Hsu P-Y, Hsu H-K, Lan X, Juan L, Yan PS, Labanowska J, Heerema N, Hsiao T-H, Chiu Y-C, Chen Y, Liu Y, Li L, Li R, Thompson IM, Nephew KP, Sharp ZD, Kirma NB, Jin VX, Huang T H-M. (2013) Amplification of distant estrogen response elements deregulates target genes associated with tamoxifen resistance in breast cancer. Cancer Cell 24:197. PMCID: PMC3890247.
Sun J, Pan H, Lei C, Yuan B, Nair SJ, April C, Parameswaran B, Klotzle B, Fan J-B, Ruan J, and Li R: (2011) Genetic and genomic analyses of an RNA polymerase II-pausing factor in regulation of mammalian transcription and cell growth. J Biol Chem. 286: 36248-57 [Epub 2011 Aug 24]. PMCID: PMC3196092.
Sun J and Li R. (2010) Human negative elongation factor activates transcription and regulates alternative transcription initiation. J Biol Chem. 285: 6443-52. [Epub 2009 Dec 22] PMCID: PMC 2825440.
Vachon CM, Sasano H, Ghosh K, Brandt KR, Watson DA, Reynolds C, Lingle WL, Goss PE, Li R, Aiyar SE, Scott CG, Pankratz VS, Santen RJ, and Ingle JN: (2010) Aromatase immunoreactivity is increased in mammographically dense regions of the breast. Breast Cancer Res Treat. 125: 243-52. [Epub 2010 Jun 5]. PMCID: PMC2997154.
Amleh A, Nair SJ, Sun J, Sutherland A, Hasty P, and Li R: (2009) Mouse cofactor of BRCA1 (Cobra1) is required for early embryogenesis. PLoS ONE, 4: e5034. PMCID: PMC2661135.
Ghosh S, Choudary A, Ghosh S, Musi N, Hu Y, and Li R: (2009) IKKb mediates cell shape-induced aromatase expression and estrogen biosynthesis in adipose stromal cells. Mol Endocrinol. 23: 662-70. PMCID: PMC2675949.
Walter M, Liang S, Ghosh S, Hornsby PJ, and Li R: (2009) Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells. Oncogene, 28: 2745-55. PMCID: PMC2806057.
Industry Relationships and Collaborations
This faculty member (or a member of their immediate family) has reported a financial interest with the health care related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.