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Qi Cao, PhD

Assistant Professor of Inflammation and Epigenetics, Institute for Academic Medicine
Assistant Member, Research Institute
Houston Methodist
Weill Cornell Medical College


Biography

Dr. Cao earned his Ph.D. in Pathology from the University of Michigan in 2008. He was a Research Investigator in the Department of Pathology at the University of Michigan before becoming a member of the Houston Methodist Research Institute in 2013. As a member of the Cancer Research Program, he is focusing on histone modification and cancer research.   

Description of Research

For the past 9 years, Dr. Cao has been dedicated to characterizing the role of EZH2 in cancer progression. Here is a sampling of his laboratory’s major discoveries:

1-EZH2 transcript and protein levels are consistently elevated in metastatic prostate cancer and aggressive breast carcinoma compared with normal epithelia. EZH2 expression is strongly associated with a metastases- and disease-free prognosis and overall survival.
2-EZH2 regulates several tumor suppressors, including ADRB2, CDH1, rap1GAP, and Slit2. EZH2 overexpression induced epithelial cell invasion and anchorage-independent growth. However, stable EZH2 knockdown inhibited tumor growth of DU145 prostate cancer cells following murine xenograft, indicating EZH2 as a potential therapeutic target for cancer. Companies (e.g., Novartis and GSK) are developing drugs against EZH2.
3-MicroRNA (miR)-101 represses EZH2. miR-101-deficiency yields EZH2 overexpression in cancer, including prostate cancer progression. CGH analysis and genomic DNA qPCR demonstrated that loss of miR-101-encoding genomic regions results in EZH2 overexpression and cancer progression. Dr. Cao was awarded the Department of Defense Prostate Cancer Research Program Fellowship for this work.
4-Dr. Cao discovered a coordinated regulation axis between PRC1 and PRC2, which are elevated in cancer. PRC2 epigenetically regulates miRNAs that repress the PRC1 proteins BMI1 and RING2. These miRNAs play critical roles in tumor growth and cancer stem cell self-renewal. In cancer, EZH2 correlates negatively with PRC2-repressed miRNAs but positively with BMI1, RING2, and their substrate ubiquityl-H2A levels. An epigenetic link between H3K27me3 and ubiquityl-H2A mediated by PRC2-regulated miRNAs was also identified.
5-Mass spectrometric analysis revealed that the PRC2 core protein EED directly interacts with BMI1 and RING1/2. EED-PRC1 interactions attenuate PRC2 histone methyltransferase activities, but enhance PRC1 E3 ubiquitin ligase activities. EED also directly recruits PRC1 to its target genomic loci, suggesting an integral role for EED as an epigenetic exchange factor coordinating PRC1 and PRC2 activities.

Areas Of Expertise

Cancer Epigenetics Prostate cancer Breast cancer microRNA
Education & Training

Postdoctoral Fellowship , Michigan Center for Translational Pathology, University of Michigan
MS , Peking University
PhD , University of Michigan
Publications

PCAT-1, a long noncoding RNA, regulates BRCA2 and controls homologous recombination in cancer
Prensner, JR, Chen, W, Iyer, MK, Cao, Q, Ma, T, Han, S, Sahu, A, Malik, R, Wilder-Romans, K, Navone, N, Logothetis, CJ, Araujo, JC, Pisters, LL, Tewari, AK, Canman, CE, Knudsen, KE, Kitabayashi, N, Rubin, MA, Demichelis, F, Lawrence, TS, Chinnaiyan, AM & Feng, FY 2014, Cancer Research, vol 74, no. 6, pp. 1651-1660. DOI: 10.1158/0008-5472.CAN-13-3159

The central role of EED in the orchestration of polycomb group complexes
Cao, Q, Wang, X, Zhao, M, Yang, R, Malik, R, Qiao, Y, Poliakov, A, Yocum, AK, Li, Y, Chen, W, Cao, X, Jiang, X, Dahiya, A, Harris, C, Feng, FY, Kalantry, S, Qin, ZS, Dhanasekaran, SM & Chinnaiyan, AM 2014, Nature Communications, vol 5, 3127. DOI: 10.1038/ncomms4127

The Long Non-Coding RNA PCAT-1 Promotes Prostate Cancer Cell Proliferation through cMyc
Prensner, JR, Chen, W, Han, S, Iyer, MK, Cao, Q, Kothari, V, Evans, JR, Knudsen, KE, Paulsen, MT, Ljungman, M, Lawrence, TS, Chinnaiyan, AM & Feng, FY 2014, Neoplasia, vol 16, no. 11, pp. 900-908. DOI: 10.1016/j.neo.2014.09.001

The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex
Prensner, JR, Iyer, MK, Sahu, A, Asangani, IA, Cao, Q, Patel, L, Vergara, IA, Davicioni, E, Erho, N, Ghadessi, M, Jenkins, RB, Triche, TJ, Malik, R, Bedenis, R, McGregor, N, Ma, T, Chen, W, Han, S, Jing, X, Cao, X, Wang, X, Chandler, B, Yan, W, Siddiqui, J, Kunju, LP, Dhanasekaran, SM, Pienta, KJ, Feng, FY & Chinnaiyan, AM 2013, Nature Genetics, vol 45, no. 11, pp. 1392-1403. DOI: 10.1038/ng.2771

Erratum: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression (Nature (2009) 457 (910-914) DOI: 10.1038/nature07762)
Sreekumar, A, Poisson, LM, Rajendiran, TM, Khan, AP, Cao, Q, Yu, J, Laxman, B, Mehra, R, Lonigro, RJ, Li, Y, Nyati, MK, Ahsan, A, Kalyana-Sundaram, S, Han, B, Cao, X, Byun, J, Omenn, GS, Ghosh, D, Pennathur, S, Alexander, DC, Berger, A, Shuster, JR, Wei, JT, Varambally, S, Beecher, C & Chinnaiyan, AM 2013, Nature, vol 499, no. 7459. DOI: 10.1038/nature12288

Erratum to Mechanistic rationale for inhibition of poly(ADP-Ribose) polymerase in ETS gene fusion-positive prostate cancer [Cancer Cell, 19 (2011) 664-678]
Brenner, JC, Ateeq, B, Li, Y, Yocum, AK, Cao, Q, Asangani, IA, Patel, S, Wang, X, Liang, H, Yu, J, Palanisamy, N, Siddiqui, J, Yan, W, Cao, X, Mehra, R, Sabolch, A, Basrur, V, Lonigro, RJ, Yang, J, Tomlins, SA, Maher, CA, Elenitoba-Johnson, KSJ, Hussain, M, Navone, NM, Pienta, KJ, Varambally, S, Feng, FY & Chinnaiyan, AM 2013, Cancer Cell, vol 23, no. 4. DOI: 10.1016/j.ccr.2013.04.005

Characterization of the EZH2-MMSET Histone Methyltransferase Regulatory Axis in Cancer
Asangani, IA, Ateeq, B, Cao, Q, Dodson, L, Pandhi, M, Kunju, LP, Mehra, R, Lonigro, RJ, Siddiqui, J, Palanisamy, N, Wu, YM, Cao, X, Kim, JH, Zhao, M, Qin, ZS, Iyer, MK, Maher, CA, Kumar-Sinha, C, Varambally, S & Chinnaiyan, AM 2013, Molecular Cell, vol 49, no. 1, pp. 80-93. DOI: 10.1016/j.molcel.2012.10.008

MicroRNA expression patterns in indeterminate inflammatory bowel disease
Lin, J, Cao, Q, Zhang, J, Li, Y, Shen, B, Zhao, Z, Chinnaiyan, AM & Bronner, MP 2013, Modern Pathology, vol 26, no. 1, pp. 148-154. DOI: 10.1038/modpathol.2012.131

Role of transcriptional corepressor CtBP1 in prostate cancer progression
Wang, R, Asangani, IA, Chakravarthi, BVSK, Ateeq, B, Lonigro, RJ, Cao, Q, Mani, RS, Camacho, DF, McGregor, N, Schumann, TEW, Jing, X, Menawat, R, Tomlins, SA, Zheng, H, Otte, AP, Mehra, R, Siddiqui, J, Dhanasekaran, SM, Nyati, MK, Pienta, KJ, Palanisamy, N, Kunju, LP, Rubin, MA, Chinnaiyan, AM & Varambally, S 2012, Neoplasia (United States), vol 14, no. 10, pp. 905-914. DOI: 10.1593/neo.121192

Role of dutasteride in pre-clinical ETS fusion-positive prostate cancer models
Ateeq, B, Vellaichamy, A, Tomlins, SA, Wang, R, Cao, Q, Lonigro, RJ, Pienta, KJ & Varambally, S 2012, Prostate, vol 72, no. 14, pp. 1542-1549. DOI: 10.1002/pros.22509

The tumor suppressor gene rap1GAP is silenced by miR-101-mediated EZH2 overexpression in invasive squamous cell carcinoma
Banerjee, R, Mani, RS, Russo, N, Scanlon, CS, Tsodikov, A, Jing, X, Cao, Q, Palanisamy, N, Metwally, T, Inglehart, RC, Tomlins, S, Bradford, C, Carey, T, Wolf, G, Kalyana-Sundaram, S, Chinnaiyan, AM, Varambally, S & DSilva, NJ 2011, Oncogene, vol 30, no. 42, pp. 4339-4349. DOI: 10.1038/onc.2011.141

Coordinated Regulation of Polycomb Group Complexes through microRNAs in Cancer
Cao, Q, Mani, RS, Ateeq, B, Dhanasekaran, SM, Asangani, IA, Prensner, JR, Kim, JH, Brenner, JC, Jing, X, Cao, X, Wang, R, Li, Y, Dahiya, A, Wang, L, Pandhi, M, Lonigro, RJ, Wu, YM, Tomlins, SA, Palanisamy, N, Qin, Z, Yu, J, Maher, CA, Varambally, S & Chinnaiyan, AM 2011, Cancer Cell, vol 20, no. 2, pp. 187-199. DOI: 10.1016/j.ccr.2011.06.016

TMPRSS2-ERG-mediated feed-forward regulation of wild-type ERG in human prostate cancers
Mani, RS, Iyer, MK, Cao, Q, Brenner, JC, Wang, L, Ghosh, A, Cao, X, Lonigro, RJ, Tomlins, SA, Varambally, S & Chinnaiyan, AM 2011, Cancer Research, vol 71, no. 16, pp. 5387-5392. DOI: 10.1158/0008-5472.CAN-11-0876

Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression
Prensner, JR, Iyer, MK, Balbin, OA, Dhanasekaran, SM, Cao, Q, Brenner, JC, Laxman, B, Asangani, IA, Grasso, CS, Kominsky, HD, Cao, X, Jing, X, Wang, X, Siddiqui, J, Wei, JT, Robinson, D, Iyer, HK, Palanisamy, N, Maher, CA & Chinnaiyan, AM 2011, Nature Biotechnology, vol 29, no. 8, pp. 742-749. DOI: 10.1038/nbt.1914

Targeting of microRNA-142-3p in dendritic cells regulates endotoxin-induced mortality
Sun, Y, Varambally, S, Maher, CA, Cao, Q, Chockley, P, Toubai, T, Malter, C, Nieves, E, Tawara, I, Wang, Y, Ward, PA, Chinnaiyan, A & Reddy, P 2011, Blood, vol 117, no. 23, pp. 6172-6183. DOI: 10.1182/blood-2010-12-325647

Characterization of KRAS rearrangements in metastatic prostate cancer
Wang, XS, Shankar, S, Dhanasekaran, SM, Ateeq, B, Sasaki, AT, Jing, X, Robinson, D, Cao, Q, Prensner, JR, Yocum, AK, Wang, R, Fries, DF, Han, B, Asangani, IA, Cao, X, Li, Y, Omenn, GS, Pflueger, D, Gopalan, A, Reuter, VE, Kahoud, ER, Cantley, LC, Rubin, MA, Palanisamy, N, Varambally, S & Chinnaiyan, AM 2011, Cancer Discovery, vol 1, no. 1, pp. 35-43. DOI: 10.1158/2159-8274.CD-10-0022

Mechanistic Rationale for Inhibition of Poly(ADP-Ribose) Polymerase in ETS Gene Fusion-Positive Prostate Cancer
Brenner, JC, Ateeq, B, Li, Y, Yocum, AK, Cao, Q, Asangani, IA, Patel, S, Wang, X, Liang, H, Yu, J, Palanisamy, N, Siddiqui, J, Yan, W, Cao, X, Mehra, R, Sabolch, A, Basrur, V, Lonigro, RJ, Yang, J, Tomlins, SA, Maher, CA, Elenitoba-Johnson, KSJ, Hussain, M, Navone, NM, Pienta, KJ, Varambally, S, Feng, FY & Chinnaiyan, AM 2011, Cancer Cell, vol 19, no. 5, pp. 664-678. DOI: 10.1016/j.ccr.2011.04.010

Therapeutic targeting of SPINK1-positive prostate cancer
Ateeq, B, Tomlins, SA, Laxman, B, Asangani, IA, Cao, Q, Cao, X, Li, Y, Wang, X, Feng, FY, Pienta, KJ, Varambally, S & Chinnaiyan, AM 2011, Science Translational Medicine, vol 3, no. 72, 72ra17. DOI: 10.1126/scitranslmed.3001498

The neuronal repellent SLIT2 is a target for repression by EZH2 in prostate cancer
Yu, J, Cao, Q, Yu, J, Wu, L, Dallol, A, Li, J, Chen, G, Grasso, C, Cao, X, Lonigro, RJ, Varambally, S, Mehra, R, Palanisamy, N, Wu, JY, Latif, F & Chinnaiyan, AM 2010, Oncogene, vol 29, no. 39, pp. 5370-5380. DOI: 10.1038/onc.2010.269

Letter to the editor
Sreekumar, A, Poisson, LM, Rajendiran, TM, Khan, AP, Cao, Q, Yu, J, Laxman, B, Mehra, R, Lonigro, RJ, Li, Y, Nyati, MK, Ahsan, A, Kalyana-Sundaram, S, Han, B, Cao, X, Byun, J, Omenn, GS, Ghoshd, D, Pennathur, S, Alexander, DC, Berger, A, Shuster, JR, Wei, JT, Varambally, S, Beecher, C & Chinnaiyan, AM 2010, European Urology, vol 58, no. 3. DOI: 10.1016/j.eururo.2010.05.003