Shengqing Gu, Ph.D.
Department of Hematopoietic Biology & Malignancy, Division of Cancer Medicine
About Dr. Shengqing Gu
Present Title & Affiliation
Primary Appointment
Assistant Professor, Department of Hematopoietic Biology and Malignancy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Faculty, The University of Texas Graduate School of Biomedical Sciences, Houston, TX
Research Interests
Our lab is interested in enhancing the efficacy of cancer immunotherapy by modulating cell-cell interactions. To achieve this goal, we integrate various cutting-edge experimental and computational approaches in the areas of functional genomics, single-cell/spatial multi-omics, data mining, machine learning, and mathematical modeling, among others. Here are several research directions in the lab:
Context-dependent gene regulation
We aim to perturb gene expression in the tumor to enhance immunotherapy with desired immunomodulatory effects. Our previous research revealed that gene expression regulation depends on the cellular genetic/epigenetic context. For example, cancer cells with different baseline NF-κB expression can show different responses to SMAC mimetics in upregulating MHC-I. Therefore, to achieve the desired immunomodulatory effects, we need rational, personalized strategies to perturb gene expression. To this end, we will integrate functional genomics, single-cell/spatial technologies, and machine learning approaches to elucidate the context-dependent gene regulation mechanisms.
Novel mechanisms of cell-cell interaction
The essence of the anti-cancer immune response lies in cell-cell interactions. Our previous research investigated multiple aspects of such interaction at different levels. We applied machine learning models to public bulk tumor gene expression data and identified SERPINB9 and MAN2A1 as regulators of cancer cells’ response to cytotoxic T cells. Using in vivo CRISPR screens, we identified a ubiquitin E3 ligase, COP1, whose inhibition can alter macrophage infiltration and sensitize tumors to immunotherapy. We also identified multiple regulators of the MHC-I/II antigen presentation machinery in cancer cells that can modulate cancer-T-cell interaction. We are interested in other cell-cell interaction mechanisms in the tumor microenvironment.
Dynamics of anti-cancer immune response
With the expanding options for cancer therapy and vast possibilities for drug scheduling, we need quantitative models of the response dynamics to rationally design combination strategies. Our previous research integrated a branching model and ODE models to simulate the dynamics of ovarian cancer clinical course and predict optimal combinations of surgery and chemotherapy for this disease. We also used clonal tracing of cancer cells to characterize the dynamics and heterogeneity of response to immune checkpoint blockade therapy. We aim to further integrate experimental/clinical data and mathematical modeling to quantify the dynamics of the anti-cancer immune response, which can help us gain mechanistic insights into this biological process and optimize combination therapy strategies.
Education & Training
Degree-Granting Education
| 2016 | University of Toronto, Ontario, CAN, PHD, Medical Biophysics |
| 2007 | Peking University, Beijing, CHN, BS, Biological Sciences |
Postgraduate Training
| 2016-2021 | Postdoctoral Fellow, Data Science, Dana-Farber Cancer Institute, Boston, MA |
Experience & Service
Academic Appointments
Instructor, Department of Medical Oncology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA, 2021 - 2022
Postdoctoral Fellow, Department of Data Science, Harvard T.H. Chan School of Public Health, Dana-Farber Cancer Institute, Boston, MA, 2016 - 2021
Other Appointments/Responsibilities
Graduate Researcher, University of Toronto, University Health Network Department of Medical Biophysics, Ontario, 2008 - 2016
Technician, Chinese Academy of Sciences - Institute of Genetics and Developmental Biology, Beijing, 2007 - 2008
Honors & Awards
| 2022 | Underrepresented Early Career Scientists Travel Award, Dana-Farber Cancer Institute |
| 2021 | SITC Annual Meeting Young Investigator Travel Award, Society for Immunotherapy of Cancer |
| 2021 | AACR-Doreen J. Putrah Cancer Research Foundation Scholar-in-Training Award, American Association for Cancer Research |
| 2015 | AACR-Marsha Rivkin Center for Ovarian Cancer Research Scholar-in-Training Award, American Association for Cancer Research |
| 2014 | Department of Medical Biophysics Doctoral Completion Award, University of Toronto |
| 2011 | Department of Medical Biophysics Travel Award, University of Toronto |
| 2011 | ORT Travel Award, University Health Network |
| 2011 | Canadian Cancer Research Conference Travel Award, Canadian Cancer Research |
| 2010 | Department of Medical Biophysics Travel Award, University of Toronto |
| 2009 | University of Toronto Award Fund, University of Toronto |
| 2004 | Peking University Principal’s Undergraduate Research Award, Peking University |
| 2004 | Beijing 21st Undergraduate Physics Contest 3rd Prize, Peking University |
Professional Memberships
Selected Publications
Peer-Reviewed Articles
- Zeng Z, Gu SS, Ouardaoui N, Tymm C, Yang L, Wong CJ, Li D, Zhang W, Wang X, Weirather JL, Rodig SJ, Hodi FS, Brown M, Liu XS. Hippo signaling pathway regulates cancer cell-intrinsic MHC-II expression. Cancer Immunol Res 10(12):1559-1569, 2022. e-Pub 2022. PMID: 36219700.
- Zeng Z, Gu SS, Wong CJ, Yang L, Ouardaoui N, Li D, Zhang W, Brown M, Liu XS. Machine learning on syngeneic mouse tumor profiles to model clinical immunotherapy response. Sci Adv 8(41):eabm8564, 2022. e-Pub 2022. PMID: 36240281.
- Aubrey BJ, Cutler JA, Bourgeois W, Donovan KA, Gu S, Hatton C, Perlee S, Perner F, Rahnamoun H, Theall ACP, Henrich JA, Zhu Q, Nowak RP, Kim YJ, Parvin S, Cremer A, Olsen SN, Eleuteri NA, Pikman Y, McGeehan GM, Stegmaier K, Letai A, Fischer ES, Liu XS, Armstrong SA. IKAROS and MENIN coordinate therapeutically actionable leukemogenic gene expression in MLL-r acute myeloid leukemia. Nat Cancer 3(5):595-613, 2022. e-Pub 2022. PMID: 35534777.
- Qiu X, Boufaied N, Hallal T, Feit A, de Polo A, Luoma AM, Alahmadi W, Larocque J, Zadra G, Xie Y, Gu S, Tang Q, Zhang Y, Syamala S, Seo JH, Bell C, O'Connor E, Liu Y, Schaeffer EM, Jeffrey Karnes R, Weinmann S, Davicioni E, Morrissey C, Cejas P, Ellis L, Loda M, Wucherpfennig KW, Pomerantz MM, Spratt DE, Corey E, Freedman ML, Shirley Liu X, Brown M, Long HW, Labbé DP. MYC drives aggressive prostate cancer by disrupting transcriptional pause release at androgen receptor targets. Nat Commun 13(1):2559, 2022. e-Pub 2022. PMID: 35562350.
- Zhou J, Wu Z, Zhang Z, Goss L, McFarland J, Nagaraja A, Xie Y, Gu S, Peng K, Zeng Y, Zhang X, Long H, Nakagawa H, Rustgi A, Diehl JA, Meyerson M, Wong KK, Bass A. Pan-ERBB kinase inhibition augments CDK4/6 inhibitor efficacy in oesophageal squamous cell carcinoma. Gut 71(4):665-675, 2022. e-Pub 2021. PMID: 33789967.
- Zhou L, Zeng Z, Egloff AM, Zhang F, Guo F, Campbell KM, Du P, Fu J, Zolkind P, Ma X, Zhang Z, Zhang Y, Wang X, Gu S, Riley R, Nakahori Y, Keegan J, Haddad R, Schoenfeld JD, Griffith O, Manguso RT, Lederer JA, Liu XS, Uppaluri R. Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders. J Immunother Cancer 10(1), 2022. PMID: 35058328.
- Zeng Z, Wong CJ, Yang L, Ouardaoui N, Li D, Zhang W, Gu S, Zhang Y, Liu Y, Wang X, Fu J, Zhou L, Zhang B, Kim S, Yates KB, Brown M, Freeman GJ, Uppaluri R, Manguso R, Liu XS. TISMO: syngeneic mouse tumor database to model tumor immunity and immunotherapy response. Nucleic Acids Res 50(D1):D1391-D1397, 2022. PMID: 34534350.
- Wang X, Tokheim C, Gu SS, Wang B, Tang Q, Li Y, Traugh N, Zeng Z, Zhang Y, Li Z, Zhang B, Fu J, Xiao T, Li W, Meyer CA, Chu J, Jiang P, Cejas P, Lim K, Long H, Brown M, Liu XS. In vivo CRISPR screens identify the E3 ligase Cop1 as a modulator of macrophage infiltration and cancer immunotherapy target. Cell 184(21):5357-5374.e22, 2021. e-Pub 2021. PMID: 34582788.
- Qiu X, Feit AS, Feiglin A, Xie Y, Kesten N, Taing L, Perkins J, Gu S, Li Y, Cejas P, Zhou N, Jeselsohn R, Brown M, Shirley Liu X, Long HW. CoBRA: Containerized Bioinformatics Workflow for Reproducible ChIP/ATAC-seq Analysis. Genomics Proteomics Bioinformatics 19(4):652-661, 2021. e-Pub 2021. PMID: 34284136.
- Gu SS, Zhang W, Wang X, Jiang P, Traugh N, Li Z, Meyer C, Stewig B, Xie Y, Bu X, Manos MP, Font-Tello A, Gjini E, Lako A, Lim K, Conway J, Tewari AK, Zeng Z, Sahu AD, Tokheim C, Weirather JL, Fu J, Zhang Y, Kroger B, Liang JH, Cejas P, Freeman GJ, Rodig S, Long HW, Gewurz BE, Hodi FS, Brown M, Liu XS. Therapeutically Increasing MHC-I Expression Potentiates Immune Checkpoint Blockade. Cancer Discov 11(6):1524-1541, 2021. e-Pub 2021. PMID: 33589424.
- Gu S, Lheureux S, Sayad A, Cybulska P, Hogen L, Vyarvelska I, Tu D, Parulekar WR, Nankivell M, Kehoe S, Chi DS, Levine DA, Bernardini MQ, Rosen B, Oza A, Brown M, Neel BG. Computational modeling of ovarian cancer dynamics suggests optimal strategies for therapy and screening. Proc Natl Acad Sci U S A 118(25), 2021. PMID: 34161278.
- Zhang S, Iyer S, Ran H, Dolgalev I, Gu S, Wei W, Foster CJR, Loomis CA, Olvera N, Dao F, Levine DA, Weinberg RA, Neel BG. Genetically Defined, Syngeneic Organoid Platform for Developing Combination Therapies for Ovarian Cancer. Cancer Discov 11(2):362-383, 2021. e-Pub 2020. PMID: 33158842.
- Wan C, Keany MP, Dong H, Al-Alem LF, Pandya UM, Lazo S, Boehnke K, Lynch KN, Xu R, Zarrella DT, Gu S, Cejas P, Lim K, Long HW, Elias KM, Horowitz NS, Feltmate CM, Muto MG, Worley MJ, Berkowitz RS, Matulonis UA, Nucci MR, Crum CP, Rueda BR, Brown M, Liu XS, Hill SJ. Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer. Cancer Res 81(1):158-173, 2021. e-Pub 2020. PMID: 33158814.
- Shi S, Gu S, Han T, Zhang W, Huang L, Li Z, Pan D, Fu J, Ge J, Brown M, Zhang P, Jiang P, Wucherpfennig KW, Liu XS. Inhibition of MAN2A1 Enhances the Immune Response to Anti-PD-L1 in Human Tumors. Clin Cancer Res 26(22):5990-6002, 2020. e-Pub 2020. PMID: 32723834.
- Gu SS, Wang X, Hu X, Jiang P, Li Z, Traugh N, Bu X, Tang Q, Wang C, Zeng Z, Fu J, Meyer C, Zhang Y, Cejas P, Lim K, Wang J, Zhang W, Tokheim C, Sahu AD, Xing X, Kroger B, Ouyang Z, Long H, Freeman GJ, Brown M, Liu XS. Clonal tracing reveals diverse patterns of response to immune checkpoint blockade. Genome Biol 21(1):263, 2020. e-Pub 2020. PMID: 33059736.
- Li Z, Wang B, Gu S, Jiang P, Sahu A, Chen CH, Han T, Shi S, Wang X, Traugh N, Liu H, Liu Y, Wu Q, Brown M, Xiao T, Boland GM, Shirley Liu X. CRISPR Screens Identify Essential Cell Growth Mediators in BRAF Inhibitor-resistant Melanoma. Genomics Proteomics Bioinformatics 18(1):26-40, 2020. e-Pub 2020. PMID: 32413516.
- Zhang J, Hu X, Wang J, Sahu AD, Cohen D, Song L, Ouyang Z, Fan J, Wang B, Fu J, Gu S, Sade-Feldman M, Hacohen N, Li W, Ying X, Li B, Liu XS. Immune receptor repertoires in pediatric and adult acute myeloid leukemia. Genome Med 11(1):73, 2019. e-Pub 2019. PMID: 31771646.
- Hu X, Zhang J, Wang J, Fu J, Li T, Zheng X, Wang B, Gu S, Jiang P, Fan J, Ying X, Zhang J, Carroll MC, Wucherpfennig KW, Hacohen N, Zhang F, Zhang P, Liu JS, Li B, Liu XS. Landscape of B cell immunity and related immune evasion in human cancers. Nat Genet 51(3):560-567, 2019. e-Pub 2019. PMID: 30742113.
- Jiang P, Gu S, Pan D, Fu J, Sahu A, Hu X, Li Z, Traugh N, Bu X, Li B, Liu J, Freeman GJ, Brown MA, Wucherpfennig KW, Liu XS. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nat Med 24(10):1550-1558, 2018. e-Pub 2018. PMID: 30127393.
- Gu S, Sayad A, Chan G, Yang W, Lu Z, Virtanen C, Van Etten RA, Neel BG. SHP2 is required for BCR-ABL1-induced hematologic neoplasia. Leukemia 32(1):203-213, 2018. e-Pub 2017. PMID: 28804122.
- Gu S, Chan WW, Mohi G, Rosenbaum J, Sayad A, Lu Z, Virtanen C, Li S, Neel BG, Van Etten RA. Distinct GAB2 signaling pathways are essential for myeloid and lymphoid transformation and leukemogenesis by BCR-ABL1. Blood 127(14):1803-13, 2016. e-Pub 2016. PMID: 26773044.
- Hatlen MA, Arora K, Vacic V, Grabowska EA, Liao W, Riley-Gillis B, Oschwald DM, Wang L, Joergens JE, Shih AH, Rapaport F, Gu S, Voza F, Asai T, Neel BG, Kharas MG, Gonen M, Levine RL, Nimer SD. Integrative genetic analysis of mouse and human AML identifies cooperating disease alleles. J Exp Med 213(1):25-34, 2016. e-Pub 2015. PMID: 26666262.
- Chan G, Gu S, Neel BG. Erk1 and Erk2 are required for maintenance of hematopoietic stem cells and adult hematopoiesis. Blood 121(18):3594-8, 2013. e-Pub 2013. PMID: 23444405.
- Wu X, Yin J, Simpson J, Kim KH, Gu S, Hong JH, Bayliss P, Backx PH, Neel BG, Araki T. Increased BRAF heterodimerization is the common pathogenic mechanism for noonan syndrome-associated RAF1 mutants. Mol Cell Biol 32(19):3872-90, 2012. e-Pub 2012. PMID: 22826437.
- Levaot N, Voytyuk O, Dimitriou I, Sircoulomb F, Chandrakumar A, Deckert M, Krzyzanowski PM, Scotter A, Gu S, Janmohamed S, Cong F, Simoncic PD, Ueki Y, La Rose J, Rottapel R. Loss of Tankyrase-mediated destruction of 3BP2 is the underlying pathogenic mechanism of cherubism. Cell 147(6):1324-39, 2011. PMID: 22153076.
- Chan G, Cheung LS, Yang W, Milyavsky M, Sanders AD, Gu S, Hong WX, Liu AX, Wang X, Barbara M, Sharma T, Gavin J, Kutok JL, Iscove NN, Shannon KM, Dick JE, Neel BG, Braun BS. Essential role for Ptpn11 in survival of hematopoietic stem and progenitor cells. Blood 117(16):4253-61, 2011. e-Pub 2011. PMID: 21398220.
Grant & Contract Support
| Title: | Novel approach to sensitize acute myeloid leukemia (AML) to immunotherapy |
| Funding Source: | PhRMA Foundation |
| Role: | Principal Investigator |
| Title: | Enhancing the efficacy of immunotherapy by optimal use of SMAC mimetics |
| Funding Source: | NIH/NCI |
| Role: | Principal Investigator |
Patient Reviews
CV information above last modified June 14, 2024