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      Sachet A. Shukla Image

      Sachet A. Shukla, PhD, MS

      Department of Hematopoietic Biology & Malignancy, Division of Cancer Medicine

      Present Title & Affiliation

      Primary Appointment

      Assistant Professor, Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX

      Assistant Professor (Joint appointment), Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX

      Research Interests

      My research studies focus on elucidating the role of the immune system in cancer biology and discovery of novel immunotherapeutic targets through development of immunogenomic approaches. Genomic analysis of immune related genes has traditionally been error-prone due to their high degree of diversity in the population. To address this problem I have developed a computational method called Polysolver for accurate typing and mutation detection in the highly polymorphic human leukocyte antigen (HLA) genes using next-generation sequencing (NGS) data (Nat Biotech, 2015).  This tool has been shown to have superlative performance characteristics and has been instrumental in characterizing patient immunophenotypes in many different cancer studies. Neoantigen based cancer vaccines constitute a novel immunotherapeutic paradigm that recruit tumor-specific cytotoxic immune responses against cancer specific peptides. I have developed a computational pipeline for the rational design of neoantigen-based vaccines (Blood, 2014) which has already been used in two first-in-man clinical trials at Dana-Farber Cancer Institute (Nature, 2017; Nature, 2019). The neoantigen prediction pipeline, in conjunction with the Polysolver tool, has also led to the identification of immunological correlates of several biological and clinical features in various tumor types (JAMA Onc, 2015; Nat Genetics, 2016; Cell Rep, 2016; Immunity, 2017). I have supervised the development of a computational pipeline for quantification of endogenous retroviruses (ERVs) in the human genome, which has identified some potentially targetable antigen targets (Nat Med, 2020). A second major focus of my work has been in delineating mechanisms of response and resistance to immune therapies, particularly checkpoint blockade (Science, 2015; JAMA Onc, 2019; Nat Med 2020). I have recently spearheaded a multi-institutional project which uncovered a novel expression signature of resistance to anti-CTLA4 therapy in metastatic melanoma with significant clinical implications (Cell, 2018). I have previously identified a metabolomic signature of response to PD-1 blockade in renal cancer and am currently developing methods for integrating metabolomic data with matched genomic, transcriptomic and immunostaining profiles (Nat Comm, 2019). I have developed pipelines for bulk and single cell T-cell receptor sequencing analysis which are currently being used in several ongoing studies designed to address fundamental questions in T-cell biology (Nature Protoc, 2019)

      Education & Training

      Degree-Granting Education

      2014Iowa State University, Ames, Iowa, US, Ph.D. in Bioinformatics and Statistics
      2006Iowa State University, Ames, Iowa, US, M.S. in Statistics
      2003Iowa State University, Ames, Iowa, US, M.S. in Bioinformatics and Computational Biology
      2000University of Pune, Pune, IN, Advanced Diploma in Bioinformatics
      1999Indian Institute of Technology, Kharagpur, IN, Bachelor of Technology in Chemical Engineering

      Experience & Service

      Other Professional Positions

      Computational Lead Scientist, Dana-Farber Cancer Institute, Boston, MA, 2018 - 2021

      Senior Scientist, Dana-Farber Cancer Institute, Boston, MA, 2014 - 2018

      Scientist II, Dana-Farber Cancer Institute, Boston, MA, 2012 - 2014

      Research Scientist, Dana-Farber Cancer Institute, Boston, MA, 2010 - 2012

      Research Analyst II, Dana-Farber Cancer Institute, Boston, MA, 2008 - 2010

      Computational Biologist, NewLink Genetics, Ames, IA, 2000 - 2008

      Honors & Awards

      2016 - 2021NCI Research Specialist Award, NIH-NCI
      2010 - 2025Highly cited researcher, Web of Science
      2005 - 2006L.H. Baker graduate award, Statistics Department, Iowa State University
      2000 - 2001Bioinformatics and Computational Biology departmental fellowship, Iowa State University
      2000 - 2001Premium for Academic Excellence Award, Iowa State University
      1999 - 2000Department of Biotechnology Fellowship, Government of India

      Professional Memberships

      American Association for Cancer Research

      2015 - Present

      Grant & Contract Support

      Date: 2025 - 2028
      Title:Discovery of non-canonical antigens in triple negative breast cancer for development of novel T cell therapies
      Funding Source:US DoD
      Role:PI
      Date: 2025 - 2028
      Title:Building T cell products in NF1-associated MPNST through antigen discovery and epigenome targeting
      Funding Source:US Department of Defense
      Role:PI
      Date: 2025 - 2026
      Title:Development of vaccine and T cell therapy for pediatric glioma patients
      Funding Source:Lindonlight Collective
      Role:PI
      ID:GA-24-008
      Date: 2024 - 2029
      Title:Translating molecular profiles into treatment approaches to target disparities in lymphoma
      Funding Source:Leukemia Lymphoma Society/Emory University
      Role:PI
      ID:Research Grant Agreement 7038-25
      Date: 2024 - 2026
      Title:Elucidating immune effector antigenic vulnerabilities in high-risk Multiple Myeloma
      Funding Source:The University of Texas MD Anderson Cancer Center
      Role:PI
      ID:00064077-Y1
      Date: 2024 - 2025
      Title:Aberrant RNA splicing by PRMT5 inhibition in Gliomas
      Funding Source:The University of Texas MD Anderson Cancer Center FY25 Cancer Neuroscience Program
      Role:PI
      Date: 2024 - 2025
      Title:Comprehensive antigen discovery in ovarian cancer for development of novel immunotherapies
      Funding Source:The University of Texas MD Anderson Cancer Center FY25 Ovarian Cancer Moonshot
      Role:PI
      Date: 2024 - 2025
      Title:A comprehensive antigen discovery pipeline for development of immunotherapy and immunoprevention approaches in pancreatic cancer
      Funding Source:The University of Texas MD Anderson Cancer Center FY25 Pediatric Cancer Moonshot
      Role:PI
      Date: 2024 - Present
      Title:Lead Discovery and Co-Development Collaboration Agreement -CureVac
      Funding Source:CSO’s office and the ECLIPSE platform
      Role:PI
      Date: 2023 - 2028
      Title:Computational toolkit for robust detection of genomic variation in human leukocyte antigen genes
      Funding Source:NIH/NIGMS
      Role:PI
      ID:R01GM152497
      Date: 2023 - 2024
      Title:Identification of non-canonical antigens for development of novel immunotherapies in glioblastoma
      Funding Source:Uncle Kory Foundation
      Role:PI
      Date: 2022 - 2023
      Title:Personalizing CAR T-cell therapy; Collaboration ID: ECLIPSE:BCell-0131
      Funding Source:M.D Anderson Moon Shot Program
      Role:Co-PI
      Date: 2022 - 2023
      Title:Discovery of Transcription Dysregulation-Derived Antigens in Colorectal Cancer
      Funding Source:UTMDACC GI SPORE DRP Program
      Role:PI
      Date: 2021 - 2026
      Title:Discovery of antigen targets for cancer immunotherapy
      Funding Source:Cancer Prevention & Research Institute of Texas (CPRIT)
      Role:PI
      ID:RR220009
      Date: 2020 - 2023
      Title:Combining Locally Administered Ipilimumab with a Personalized Neoantigen Cancer Vaccine to Improve T-Cell Priming and Antitumor Immunity in High-Risk Renal Cell Carcinoma
      Funding Source:Department of Defense (DOD)
      Role:CO-I
      ID:W81XWH-20-1-0533 (KC190130P1)
      Date: 2020 - 2024
      Title:DF/HCC Kidney Cancer SPORE
      Funding Source:NIH/NCI
      Role:CO-I
      ID:P50CA101942
      Date: 2020 - 2021
      Title:Tissue-based predictive biomarkers for Cabozantinib therapy in metastatic renal cell carcinoma
      Funding Source:NIH/NCI
      Role:CO-I
      ID:R21CA238053
      Date: 2019 - 2024
      Title:Biomaterials to Create T Cell Immunity
      Funding Source:NIH/NCI
      Role:CO-I
      ID:5U54CA244726
      Date: 2018 - 2021
      Title:Using Single-Cell Transcriptomics to Understand Tumor and Immune Heterogeneity Driving Resistance to Immune Therapy in Advanced RCC
      Funding Source:Department of Defense (DOD)
      Role:CO-I
      ID:W81XWH-18-1-0367
      Date: 2016 - 2021
      Title:Immunogenomic analytical approaches for research and clinical applications
      Funding Source:NIH/NCI
      Role:PI
      ID:R50CA211482
      Date: 2011 - 2016
      Title:Personal tumor neoantigens for immunity against chronic lymphocytic leukemia
      Funding Source:NIH/NCI
      Role:Lead Scientist
      ID:R01CA155010

      Selected Publications

      Peer-Reviewed Articles

      1. Gordon BK, Muhowski EM, Singh J, Ravikrishnan J, Peris-Cuesta A, Diaz Rohena D, Sanchez JR, Thangavadivel S, Benrashid S, He A, Marr AR, Mitchell AD, Urrutia JM, Misra S, Lai TH, Yu L, Walker BR, Perry E, Shukla SA, Grieselhuber NR, Rogers KA, Lapalombella R, Blachly JS, Kittai AS, Bhat SA, Jain N, Wierda WG, Byrd JC, Niesman M, Zhang K, Sampath D, Woyach JA. PKCbeta inhibitor MS-553 displays preclinical efficacy in both treatment-naive and BTK inhibitor-resistant Chronic Lymphocytic Leukemia. Blood Cancer Discov, 2026. e-Pub 2026. PMID: 41190953.
      2. Blass, E, Keskin, DB, Tu, CR, Forman, C, Vanasse, AP, Sax, HE, Shim, B, Chea, VA, Kim, N, Carulli, IP, Southard, J, Lyu, H, Lu, W, Rickles-Young, M, Afeyan, AB, Olive, O, Mehndiratta, A, Greenslade, H, Shetty, K, Baginska, J, Gomez Diaz, I, Nau, A, Pfaff, KL, Gans, A, Ranasinghe, S, Buchbinder, E, Sussman, TA, Insco, ML, Yoon, CH, Rodig, SJ, Shukla, SA, Li, S, Aster, JC, Braun, DA, Cibulskis, C, Hacohen, N, Neuberg, D, Giobbie-Hurder, A, Livak, KJ, Fritsch, E, Oliveira, G, Simon, JM, Wu, C, Ott, PA. A multi-adjuvant personal neoantigen vaccine generates potent immunity in melanoma. Cell 188(19):5125-5141.e27, 2025. e-Pub 2025. PMID: 40645179.
      3. Labaki C, Saad E, Madsen KN, Hobeika C, Bi K, Alchoueiry M, Camp S, Hou Y, Bakouny Z, Matar S, El Ahmar N, Nyman J, Zhang L, Priolo C, Rout R, Daou M, Khabibullin D, Salem S, Schindler N, Saliby RM, Meli K, Wells JC, Pimenta E, Takemura K, Park J, Eid M, Semaan K, Fu J, Denize T, El Hajj Chehade R, Machaalani M, Nawfal R, Khatoun WD, eh M, El Masri J, Haddad NR, Xu W, McGregor BA, Hirsch MS, Xie W, Heng DYC, McDermott DF, Signoretti S, Van Allen EM, Shukla SA, Choueiri TK, Henske EP, Braun DA. Tumor-Intrinsic and Microenvironmental Determinants of Impaired Antitumor Immunity in Chromophobe Renal Cell Carcinoma. Journal of Clinical Oncology 43(23):2639-2654, 2025. e-Pub 2025. PMID: 40601888.
      4. McCurry D, Ge Z, Lee J, Pasumarthi R, Leng X, Koehnke T, Pasvolsky O, Raparla P, Nguyen V, Maurer K, Li S, Livak KJ, Danson E, Thakkar B, Azizi E, Soiffer RJ, Shukla SA, Majeti R, Ritz J, Wu CJ, Molldrem JJ, Bachireddy P. ASXL1 truncating mutations drive leukemic resistance to T cell attack. bioRxiv, 2025. e-Pub 2025. PMID: 40661385.
      5. Hamada, T, Ugai, T, Gurjao, C, Ugai, S, Zhang, X, Haruki, K, Takashima, Y, Akimoto, N, Lau, MC, Matsuda, K, Nakazawa, N, Higashioka, M, Miyahara, S, Kosumi, K, Masugi, Y, Liu, L, Cao, Y, Nevo, D, Wang, M, Nishihara, R, Shukla, SA, Wu, C, Garraway, LA, Meyerhardt, JA, Giovannucci, E, Nowak, JA, Fuchs, C, Chan, AT, Song, M, Giannakis, M, Ogino, S. Smoking habit and long-term colorectal cancer incidence by exome-wide mutational and neoantigen loads. BMJ Oncology 4(1), 2025. e-Pub 2025. PMID: 40519220.
      6. Jiang Q, Braun DA, Clauser KR, Ramesh V, Shirole NH, Duke-Cohan JE, Nabilsi N, Kramer NJ, Forman C, Lippincott IE, Klaeger S, Phulphagar KM, Chea V, Kim N, Vanasse AP, Saad E, Parsons T, Carr-Reynolds M, Carulli I, Pinjusic K, Jiang Y, Li R, Syamala S, Rachimi S, Verzani EK, Stevens JD, Lane WJ, Camp SY, Meli K, Pappalardi MB, Herbert ZT, Qiu X, Cejas P, Long HW, Shukla SA, Van Allen EM, Choueiri TK, Churchman LS, Abelin JG, Gurer C, MacBeath G, Childs RW, Carr SA, Keskin DB, Wu CJ, Kaelin WG Jr. HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy. Cell 188(7):1807-1827.e34, 2025. e-Pub 2025. PMID: 40023154.
      7. Braun DA, Moranzoni G, Chea V, McGregor BA, Blass E, Tu CR, Vanasse AP, Forman C, Forman J, Afeyan AB, Schindler NR, Liu Y, Li S, Southard J, Chang SL, Hirsch MS, LeBoeuf NR, Olive O, Mehndiratta A, Greenslade H, Shetty K, Klaeger S, Sarkizova S, Pedersen CB, Mossanen M, Carulli I, Tarren A, Duke-Cohan J, Howard AA, Iorgulescu JB, Shim B, Simon JM, Signoretti S, Aster JC, Elagina L, Carr SA, Leshchiner I, Getz G, Gabriel S, Hacohen N, Olsen LR, Oliveira G, Neuberg DS, Livak KJ, Shukla SA, Fritsch EF, Wu CJ, Keskin DB, Ott PA, Choueiri TK. A neoantigen vaccine generates antitumour immunity in renal cell carcinoma. Nature 639(8054):474-482, 2025. e-Pub 2025. PMID: 39910301.
      8. Xu W, Birch G, Meliki A, Moritz V, Bharadwaj M, Schindler NR, Labaki C, Saliby RM, Dinh K, Horst JT, Sun M, Kashima S, Hugaboom M, Dighe A, Machaalani M, Lee GM, Hurwitz M, McGregor BA, Hirsch MS, Shukla SA, McDermott DF, Signoretti S, Romee R, Choueiri TK, Braun DA. Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes. ESMO Open 10(2):104105, 2025. e-Pub 2025. PMID: 39813824.
      9. Jammihal T, Saliby RM, Labaki C, Soulati H, Gallegos J, Peris A, McCurry D, Yu C, Shah V, Poduval D, El Zarif T, El Ahmar N, Laimon YN, Eid M, Sheshdeh AB, Krajewski KM, Buttner FA, Schwab M, Heng D, Casellas RC, Rai K, Zacharias Millward NM, Msaouel P, Karam J, Signoretti S, Van Allen E, Choueiri TK, Braun DA, Shukla SA. Immunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma. Nat Cancer 6(2):372-384, 2025. e-Pub 2025. PMID: 39789182.
      10. Parry, EM, Lemvigh, C, Deng, S, Dangle, N, Ruthen, NG, Knisbacher, BA, Broséus, J, Hergalant, S, Guièze, R, Li, S, Zhang, W, Johnson, C, Long, JM, Yin, S, Werner, L, Anandappa, AJ, Purroy, N, Gohil, SH, Oliveira, G, Bachireddy, P, Shukla, SA, Huang, T, Khoury, J, Thakral, B, Dickinson, M, Tam, C, Livak, KJ, Getz, G, Neuberg, D, Feugier, P, Kharchenko, PV, Wierda, WG, Olsen, LR, Jain, N, Wu, C. ZNF683 marks a CD8+ T cell population associated with anti-tumor immunity following anti-PD-1 therapy for Richter syndrome. Cancer cell 41(10):1803-1816.e8, 2023. e-Pub 2023. PMID: 37738974.
      11. Lai TH, Ozer HG, Gasparini P, Nigita G, Distefano R, Yu L, Ravikrishnan J, Yilmaz S, Gallegos J, Shukla S, Puduvalli V, Woyach J, Lapalombella R, Blachly J, Byrd JC, Sampath D. HDAC1 regulates the chromatin landscape to control transcriptional dependencies in chronic lymphocytic leukemia. Blood Adv 7(12):2897-2911, 2023. e-Pub 2023. PMID: 36287107.
      12. Nassar AH, Abou Alaiwi S, Baca SC, Adib E, Corona RI, Seo JH, Fonseca MAS, Spisak S, El Zarif T, Tisza V, Braun DA, Du H, He M, Flaifel A, Alchoueiry M, Denize T, Matar SG, Acosta A, Shukla S, Hou Y, Steinharter J, Bouchard G, Berchuck JE, O'Connor E, Bell C, Nuzzo PV, Mary Lee GS, Signoretti S, Hirsch MS, Pomerantz M, Henske E, Gusev A, Lawrenson K, Choueiri TK, Kwiatkowski DJ, Freedman ML. Epigenomic charting and functional annotation of risk loci in renal cell carcinoma. Nat Commun 14(1):346, 2023. e-Pub 2023. PMID: 36681680.
      13. Groha S, Alaiwi SA, Xu W, Naranbhai V, Nassar AH, Bakouny Z, El Zarif T, Saliby RM, Wan G, Rajeh A, Adib E, Nuzzo PV, Schmidt AL, Labaki C, Ricciuti B, Alessi JV, Braun DA, Shukla SA, Keenan TE, Van Allen E, Awad MM, Manos M, Rahma O, Zubiri L, Villani AC, Fairfax B, Hammer C, Khan Z, Reynolds K, Semenov Y, Schrag D, Kehl KL, Freedman ML, Choueiri TK, Gusev A. Germline variants associated with toxicity to immune checkpoint blockade. Nat Med 28(12):2584-2591, 2022. e-Pub 2022. PMID: 36526723.
      14. Denize T, Hou Y, Pignon JC, Walton E, West DJ, Freeman GJ, Braun DA, Wu CJ, Gupta S, Motzer RJ, Atkins MB, McDermott D, Choueiri TK, Shukla SA, Signoretti S. Transcriptomic Correlates of Tumor Cell PD-L1 Expression and Response to Nivolumab Monotherapy in Metastatic Clear Cell Renal Cell Carcinoma. Clin Cancer Res 28(18):4045-4055, 2022. e-Pub 2022. PMID: 35802667.
      15. Barroso-Sousa R, Forman J, Collier K, Weber ZT, Jammihal TR, Kao KZ, Richardson ET, Keenan T, Cohen O, Manos MP, Brennick RC, Ott PA, Hodi FS, Dillon DA, Attaya V, O'Meara T, Lin NU, Van Allen EM, Rodig S, Winer EP, Mittendorf EA, Wu CJ, Wagle N, Stover DG, Shukla SA, Tolaney SM. Multidimensional Molecular Profiling of Metastatic Triple-Negative Breast Cancer and Immune Checkpoint Inhibitor Benefit. JCO Precis Oncol 6:e2100413, 2022. e-Pub 2022. PMID: 35797509.
      16. Baldominos P, Barbera-Mourelle A, Barreiro O, Huang Y, Wight A, Cho JW, Zhao X, Estivill G, Adam I, Sanchez X, McCarthy S, Schaller J, Khan Z, Ruzo A, Pastorello R, Richardson ET, Dillon D, Montero-Llopis P, Barroso-Sousa R, Forman J, Shukla SA, Tolaney SM, Mittendorf EA, von Andrian UH, Wucherpfennig KW, Hemberg M, Agudo J. Quiescent cancer cells resist T cell attack by forming an immunosuppressive niche. Cell 185(10):1694-1708.e19, 2022. e-Pub 2022. PMID: 35447074.
      17. Ouspenskaia T, Law T, Clauser KR, Klaeger S, Sarkizova S, Aguet F, Li B, Christian E, Knisbacher BA, Le PM, Hartigan CR, Keshishian H, Apffel A, Oliveira G, Zhang W, Chen S, Chow YT, Ji Z, Jungreis I, Shukla SA, Justesen S, Bachireddy P, Kellis M, Getz G, Hacohen N, Keskin DB, Carr SA, Wu CJ, Regev A. Unannotated proteins expand the MHC-I-restricted immunopeptidome in cancer. Nat Biotechnol 40(2):209-217, 2022. e-Pub 2022. PMID: 34663921.
      18. Naranbhai V, Viard M, Dean M, Groha S, Braun DA, Labaki C, Shukla SA, Yuki Y, Shah P, Chin K, Wind-Rotolo M, Mu XJ, Robbins PB, Gusev A, Choueiri TK, Gulley JL, Carrington M. HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study. Lancet Oncol 23(1):172-184, 2022. e-Pub 2022. PMID: 34895481.
      19. Zeng Z, Fu J, Cibulskis C, Jhaveri A, Gumbs C, Das B, Sanchez-Espiridion B, Janssens S, Taing L, Wang J, Lindsay J, Vilimas T, Zhang J, Tokheim C, Sahu A, Jiang P, Yan C, Duose DY, Cerami E, Chen L, Cohen D, Chen Q, Enos R, Huang X, Lee JJ, Liu Y, Neuberg DS, Nguyen C, Patterson C, Sarkar S, Shukla S, Tang M, Tsuji J, Uduman M, Wang X, Weirather JL, Yu J, Yu J, Zhang J, Zhang J, Meerzaman D, Thurin M, Futreal A, Karlovich C, Gabriel SB, Wistuba II, Liu XS, Wu CJ. Cross-Site Concordance Evaluation of Tumor DNA and RNA Sequencing Platforms for the CIMAC-CIDC Network. Clin Cancer Res 27(18):5049-5061, 2021. e-Pub 2021. PMID: 33323402.
      20. Oliveira G, Stromhaug K, Klaeger S, Kula T, Frederick DT, Le PM, Forman J, Huang T, Li S, Zhang W, Xu Q, Cieri N, Clauser KR, Shukla SA, Neuberg D, Justesen S, MacBeath G, Carr SA, Fritsch EF, Hacohen N, Sade-Feldman M, Livak KJ, Boland GM, Ott PA, Keskin DB, Wu CJ. Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma. Nature 596(7870):119-125, 2021. e-Pub 2021. PMID: 34290406.
      21. Adib E, Nassar AH, Akl EW, Abou Alaiwi S, Nuzzo PV, Mouhieddine TH, Sonpavde G, Haddad RI, Mouw KW, Giannakis M, Hodi FS, Shukla SA, Gusev A, Braun DA, Choueiri TK, Kwiatkowski DJ. CDKN2A Alterations and Response to Immunotherapy in Solid Tumors. Clin Cancer Res 27(14):4025-4035, 2021. e-Pub 2021. PMID: 34074656.
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      Letters to the Editor

      1. Saliby RM, Labaki C, Jammihal TR, Xie W, Sun M, Shah V, Saad E, Kane MH, Kashima S, Sadak K, El Zarif T, Poduval D, Motzer RJ, Powles T, Rini BI, Albiges L, Pal SK, McGregor BA, McKay RR, Signoretti S, Van Allen EM, Shukla SA, Choueiri TK, Braun DA. Impact of renal cell carcinoma molecular subtypes on immunotherapy and targeted therapy outcomes. Cancer Cell 42: 732-735, 2024.
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