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INFORMATION FOR

David A. Braun, MD, PhD

Assistant Professor of Medicine (Medical Oncology), Louis Goodman and Alfred Gilman Yale Scholar

Contact Information

David A. Braun, MD, PhD

Lab Location

Mailing Address

  • Yale School of Medicine

    333 Cedar St, PO Box 208028

    New Haven, CT 06520

    United States

Research Summary

Dr. Braun's laboratory integrates experimental and computational approaches to biomedical research and is currently studying mechanisms of response and resistance to immune therapy in kidney cancer.

Extensive Research Description

How do somatic alterations impact response to immunotherapy?
We integrate genomic, transcriptomic, and immunopathologic analyses with demographic and clinical response data to dissect how tumor genetic features contribute to response or resistance to current immunotherapies, with a focus on immune checkpoint inhibitors (for example, see Braun et al, Nature Medicine, 2020 and Braun et al, JAMA Oncology, 2019)


How does the immune microenvironment impact anti-tumor immunity?
The tumor-immune microenvironment is comprised of heterogeneous cell types that may positively or negatively impact anti-tumor immune responses. Our prior work identified key immune cell populations and cellular interaction circuits that were enriched in advanced kidney cancer (see Braun et al, Cancer Cell, 2021). We now aim to utilize single-cell proteogenomic tools to systematically dissect this complex ecosystem and identify candidate immune cell populations and cellular states that impact response or resistance to immune checkpoint inhibitors. Further, we aim to construct patient-derived model systems to enable a mechanistic understanding of these potential determinants of anti-tumor immunity.


What are the target tumor antigens and what are the characteristics of T cells that recognize them?
The heart of antigen-specific anti-tumor immunity is the interaction between the T cell receptor (TCR) expressed on the surface of tumor-infiltrating T cells (TILs) and the peptide-MHC complex, displayed on a tumor cell. However, in renal cell carcinoma (RCC) and many other cancer types, the important tumor antigens and the T cells that recognize them remain largely unknown. We aim to identify relevant tumor antigens that can ultimately enable innovative “precision” approaches to cancer immunotherapies (for example, see our personalized neoantigen vaccine in RCC, NCT02950766, Co-PIs: Braun, Choueiri, Ott)


Coauthors

Research Interests

Antigens; Carcinoma, Renal Cell; Immunotherapy; Cancer Vaccines; Genomics; Tumor Microenvironment; Transcriptome

Selected Publications

  • Systematic Identification of Autosomal and Y-Encoded Minor Histocompatibility Antigens Reveals Predictors of Chronic Gvhd and Candidate GVL TargetsCieri N, Hookeri N, Stromhaug K, Stevens J, Kooshesh K, Klaeger S, Clauser K, Sarkizova S, Braun D, Penter L, Oliveira G, Kim H, Lane W, Li S, Livak K, Ho V, Ritz J, Soiffer R, Keskin D, Stewart C, Gusev A, Getz G, Wu C. Systematic Identification of Autosomal and Y-Encoded Minor Histocompatibility Antigens Reveals Predictors of Chronic Gvhd and Candidate GVL Targets Blood 2022, 140: 4762-4764. DOI: 10.1182/blood-2022-162841.
  • 115 Spatial dissection of T cell clonotype identity, transcriptional profiles, and cell-cell interactions in the tumor microenvironment and tertiary lymphoid structuresIorgulescu B, Liu S, Li S, Borji M, Barrera-Lopez I, Shanmugam V, Lyu H, Morriss J, Garcia Z, Murray E, Reardon D, Yoon C, Braun D, Livak K, Wu C, Chen F. 115 Spatial dissection of T cell clonotype identity, transcriptional profiles, and cell-cell interactions in the tumor microenvironment and tertiary lymphoid structures 2022, a127-a127. DOI: 10.1136/jitc-2022-sitc2022.0115.
  • 252P Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) as intermediate endpoints for survival in metastatic breast cancer: A real-world experienceLabaki C, Bakouny Z, Sanglier T, Schmidt A, Shim J, Braun D, Bouquet F, Joyce M, Xie W, Tolaney S, Choueiri T. 252P Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) as intermediate endpoints for survival in metastatic breast cancer: A real-world experience Annals Of Oncology 2022, 33: s652. DOI: 10.1016/j.annonc.2022.07.291.
  • Dual CDKN2A/MTAP loss compared to CDKN2A loss alone and response to immune-checkpoint inhibitors (ICI) in advanced solid tumors.Adib E, Nassar A, El Zarif T, Kale N, Rakaee M, Mouhieddine T, Abou Alaiwi S, Freeman D, Labban M, Akl E, Haddad R, Hodi F, Sonpavde G, Giannakis M, Braun D, Gusev A, Choueiri T, Overstreet E, Stone E, Kwiatkowski D. Dual CDKN2A/MTAP loss compared to CDKN2A loss alone and response to immune-checkpoint inhibitors (ICI) in advanced solid tumors. Journal Of Clinical Oncology 2022, 40: 2622-2622. DOI: 10.1200/jco.2022.40.16_suppl.2622.
  • Cross-trial validation of molecular subtypes in patients with metastatic clear cell renal cell carcinoma (RCC): The JAVELIN Renal 101 experience.Saliby R, Jammihal T, Labaki C, Xie W, Motzer R, Powles T, Rini B, Albiges L, Pal S, McKay R, Signoretti S, Shukla S, Van Allen E, Braun D, Choueiri T. Cross-trial validation of molecular subtypes in patients with metastatic clear cell renal cell carcinoma (RCC): The JAVELIN Renal 101 experience. Journal Of Clinical Oncology 2022, 40: 4531-4531. DOI: 10.1200/jco.2022.40.16_suppl.4531.
  • Molecular characterization of the tumor microenvironment in chromophobe renal cell carcinoma (ChRCC) and related oncocytic neoplasms.Labaki C, Zhang L, Hou Y, Bi K, Hobeika C, Bakouny Z, Camp S, Priolo C, Khabibullin D, Schindler N, Alchoueiry M, Denize T, Saliby R, Matar S, Signoretti S, Van Allen E, Shukla S, Braun D, Henske E, Choueiri T. Molecular characterization of the tumor microenvironment in chromophobe renal cell carcinoma (ChRCC) and related oncocytic neoplasms. Journal Of Clinical Oncology 2022, 40: 4549-4549. DOI: 10.1200/jco.2022.40.16_suppl.4549.
  • Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) as intermediate endpoints for survival in metastatic breast cancer: A real-world experience.Labaki C, Bakouny Z, Sanglier T, Schmidt A, Shim J, Braun D, Bouquet F, Joyce M, Xie W, Tolaney S, Choueiri T. Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) as intermediate endpoints for survival in metastatic breast cancer: A real-world experience. Journal Of Clinical Oncology 2022, 40: 6520-6520. DOI: 10.1200/jco.2022.40.16_suppl.6520.
  • Single cell transcriptomic characterization of natural killer (NK) cell populations in clear cell renal cell carcinoma and association with clinical outcomes.Xu W, Bharadwaj M, Birch G, Schindler N, Labaki C, Saliby R, Bakouny Z, Freeman D, O'Toole J, Lee G, McGregor B, Hirsch M, Shukla S, McDermott D, Signoretti S, Romee R, Choueiri T, Braun D. Single cell transcriptomic characterization of natural killer (NK) cell populations in clear cell renal cell carcinoma and association with clinical outcomes. Journal Of Clinical Oncology 2022, 40: e16521-e16521. DOI: 10.1200/jco.2022.40.16_suppl.e16521.
  • Fumarate hydratase-deficient renal cell carcinoma: The real-world experience at Dana-Farber Cancer Institute and Moores Cancer Center.Saliby R, Labaki C, Xie W, Nonato T, Schmidt A, Bakouny Z, Xu W, Ravi P, Braun D, Hirsch M, McKay R, Choueiri T, McGregor B. Fumarate hydratase-deficient renal cell carcinoma: The real-world experience at Dana-Farber Cancer Institute and Moores Cancer Center. Journal Of Clinical Oncology 2022, 40: e16522-e16522. DOI: 10.1200/jco.2022.40.16_suppl.e16522.
  • Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced clear cell renal cell (HCRN GU16-260-Cohort A): Final report.Atkins M, Jegede O, Haas N, McDermott D, Bilen M, Stein M, Sosman J, Alter R, Plimack E, Ornstein M, Hurwitz M, Peace D, Signoretti S, Denize T, Cimadamore A, Braun D, Wu C, Einstein D, Catalano P, Hammers H. Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced clear cell renal cell (HCRN GU16-260-Cohort A): Final report. Journal Of Clinical Oncology 2022, 40: 288-288. DOI: 10.1200/jco.2022.40.6_suppl.288.
  • 76 Spatial mapping of T cell receptors and transcriptomes in renal cell carcinoma following immune checkpoint inhibitor therapyLiu S, Iorgulescu B, Li S, Morriss J, Borji M, Murray E, Braun D, Livak K, Wu C, Chen F. 76 Spatial mapping of T cell receptors and transcriptomes in renal cell carcinoma following immune checkpoint inhibitor therapy Journal For ImmunoTherapy Of Cancer 2021, 9: a84-a85. DOI: 10.1136/jitc-2021-sitc2021.076.
  • 655 Landscape of helper and regulatory CD4+ T cells in melanomaOliveira G, Stromhaug K, Klaeger S, Cieri N, Iorgulescu B, Li S, Braun D, Neuberg D, Carr S, Livak K, Tompers D, Fritsch E, Wind-Rotolo M, Hacohen N, Sade-Feldman M, Keskin D, Ott P, Rodig S, Boland G, Wu C. 655 Landscape of helper and regulatory CD4+ T cells in melanoma Journal For ImmunoTherapy Of Cancer 2021, 9: a684-a684. DOI: 10.1136/jitc-2021-sitc2021.655.
  • Abstract 62: Development of dual-targeted fine-tuned immune restoring (DFIR) CAR T cell therapy for clear cell renal cell carcinoma (ccRCC)Wang Y, Buck A, Grimaud M, Kodangattil S, Razimbaud C, Fayed A, Chang M, Culhane A, Braun D, Choueiri T, Wu C, Wei K, Chan L, Piel B, Ivanova E, Paweletz C, Barbie D, Jennings R, Ficial M, Sticco-Ivins M, Signoretti S, Freeman G, Zhu Q, Marasco W. Abstract 62: Development of dual-targeted fine-tuned immune restoring (DFIR) CAR T cell therapy for clear cell renal cell carcinoma (ccRCC) Cancer Research 2021, 81: 62-62. DOI: 10.1158/1538-7445.am2021-62.
  • Effect of high-dose corticosteroid use on efficacy of immune checkpoint inhibitors in patients with renal cell carcinoma (RCC).Labaki C, Alaiwi S, Schmidt A, Zarif T, Bakouny Z, Nuzzo P, Xu W, Braun D, McGregor B, Choueiri T. Effect of high-dose corticosteroid use on efficacy of immune checkpoint inhibitors in patients with renal cell carcinoma (RCC). Journal Of Clinical Oncology 2021, 39: 4583-4583. DOI: 10.1200/jco.2021.39.15_suppl.4583.
  • Cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) (CaNI) for advanced renal cell carcinoma with variant histology (aRCCVH).McGregor B, Xie W, Bilen M, Braun D, Xu W, Ravi P, Heath E, McDermott D, McKay R, Hammers H, Choueiri T. Cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) (CaNI) for advanced renal cell carcinoma with variant histology (aRCCVH). Journal Of Clinical Oncology 2021, 39: tps4592-tps4592. DOI: 10.1200/jco.2021.39.15_suppl.tps4592.
  • Achieve clear cell renal cell carcinoma (CCRCC) cures through dual-targeted fine-tuned immune restoring (DFIR) CAR-T cell therapyWang Y, Buck A, Grimaud M, Kodangattil S, Razimbaud C, Fayed A, Chang M, Culhane A, Braun D, Choueiri T, Wu C, Wei K, Chan L, Piel B, Ivanova E, Paweletz C, Barbie D, Jenning R, Ficial M, Sticco-Ivins M, Signoretti S, Freeman G, Zhu Q, Marasco W. Achieve clear cell renal cell carcinoma (CCRCC) cures through dual-targeted fine-tuned immune restoring (DFIR) CAR-T cell therapy Cytotherapy 2021, 23: s93. DOI: 10.1016/s1465324921004126.
  • Abstract NG13: Metabolomic adaptations and correlates of survival to immune checkpoint blockadeLi H, Bullock K, Gurjao C, Braun D, Shukla S, Bosse D, Lalani A, Gopal S, Jin C, Horak C, Wind-Rotolo M, Signoretti S, McDermott D, Freeman G, Van Allen E, Schreiber S, Hodi F, Sellers W, Garraway L, Clish C, Choueiri T, Giannakis M. Abstract NG13: Metabolomic adaptations and correlates of survival to immune checkpoint blockade Cancer Research 2020, 80: ng13-ng13. DOI: 10.1158/1538-7445.am2020-ng13.
  • Optimized management of nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal cell carcinoma (RCC): A response-based phase II study (OMNIVORE).McKay R, Xie W, McGregor B, Braun D, Wei X, Kyriakopoulos C, Zakharia Y, Maughan B, Rose T, Stadler W, McDermott D, Harshman L, Choueiri T. Optimized management of nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal cell carcinoma (RCC): A response-based phase II study (OMNIVORE). Journal Of Clinical Oncology 2020, 38: 5005-5005. DOI: 10.1200/jco.2020.38.15_suppl.5005.
  • Immunogenomic characterization of advanced clear cell renal cell carcinoma treated with PD-1 blockade.Braun D, Hou Y, Bakouny Z, Ficial M, Sant'Angelo M, Ross-Macdonald P, Jegede O, Sun M, Wind-Rotolo M, Pignon J, Neuberg D, Catalano P, Freeman G, Sharpe A, McDermott D, Van Allen E, Signoretti S, Wu C, Shukla S, Choueiri T. Immunogenomic characterization of advanced clear cell renal cell carcinoma treated with PD-1 blockade. Journal Of Clinical Oncology 2020, 38: 5010-5010. DOI: 10.1200/jco.2020.38.15_suppl.5010.
  • Evaluation of predictive biomarkers for nivolumab in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) from the CheckMate-025 (CM-025) trial.Ficial M, Jegede O, Sant'Angelo M, Moreno S, Braun D, Wind-Rotolo M, Pignon J, Catalano P, Sun M, Van Allen E, Freeman G, Sharpe A, Hodi F, Motzer R, Wu C, Atkins M, McDermott D, Shukla S, Choueiri T, Signoretti S. Evaluation of predictive biomarkers for nivolumab in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) from the CheckMate-025 (CM-025) trial. Journal Of Clinical Oncology 2020, 38: 5023-5023. DOI: 10.1200/jco.2020.38.15_suppl.5023.
  • Safety and efficacy of retreatment with immune checkpoint inhibitors (ICIs) in patients with metastatic RCC (mRCC) who have previously received an ICI.Ravi P, Bakouny Z, Flippot R, Braun D, Abou Alaiwi S, Wei X, McGregor B, Kilbridge K, Choudhury A, Harshman L, Choueiri T. Safety and efficacy of retreatment with immune checkpoint inhibitors (ICIs) in patients with metastatic RCC (mRCC) who have previously received an ICI. Journal Of Clinical Oncology 2020, 38: 698-698. DOI: 10.1200/jco.2020.38.6_suppl.698.
  • Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma (S/R RCC) to reveal potential determinants of poor prognosis and response to immune checkpoint inhibitors (ICI).Bakouny Z, Braun D, Shukla S, Pan W, Gao X, Hou Y, Flaifel A, Nassar A, Abou Alaiwi S, Flippot R, Steinharter J, Nuzzo P, Ishii Y, Ross-Macdonald P, Lee G, McDermott D, Heng D, Signoretti S, Van Allen E, Choueiri T. Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma (S/R RCC) to reveal potential determinants of poor prognosis and response to immune checkpoint inhibitors (ICI). Journal Of Clinical Oncology 2020, 38: 715-715. DOI: 10.1200/jco.2020.38.6_suppl.715.
  • Soluble PD-L1 as a marker of progressive disease on nivolumab in kidney cancer.Mahoney K, Ross-Macdonald P, Shukla S, Braun D, Song L, Veras E, Wind-Rotolo M, Van Allen E, McDermott D, Hodi F, Choueiri T, Freeman G. Soluble PD-L1 as a marker of progressive disease on nivolumab in kidney cancer. Journal Of Clinical Oncology 2020, 38: 746-746. DOI: 10.1200/jco.2020.38.6_suppl.746.
  • Circulating immune cell populations and cytokines in patients with metastatic variant histology renal cell carcinoma (vRCC) treated with atezolizumab plus bevacizumab (AB): Dynamic changes on therapy and association with outcomes from a phase II trial.Flippot R, Bakouny Z, Wei X, Braun D, McGregor B, Steinharter J, Harshman L, Vaishampayan U, Severgnini M, McDermott D, Hodi F, Lee G, Van Allen E, Signoretti S, Choueiri T, McKay R. Circulating immune cell populations and cytokines in patients with metastatic variant histology renal cell carcinoma (vRCC) treated with atezolizumab plus bevacizumab (AB): Dynamic changes on therapy and association with outcomes from a phase II trial. Journal Of Clinical Oncology 2020, 38: 740-740. DOI: 10.1200/jco.2020.38.6_suppl.740.
  • Association of polybromo-associated BAF (PBAF) complex mutations with overall survival (OS) in cancer patients (pts) treated with checkpoint inhibitors (ICIs).Abou Alaiwi S, Nassar A, El Bakouny Z, Berchuck J, Nuzzo P, Flippot R, Flaifel A, Steinharter J, Baca S, Margolis C, Vokes N, Du H, Shukla S, Braun D, Signoretti S, Sonpavde G, Kwiatkowski D, Van Allen E, Choueiri T. Association of polybromo-associated BAF (PBAF) complex mutations with overall survival (OS) in cancer patients (pts) treated with checkpoint inhibitors (ICIs). Journal Of Clinical Oncology 2019, 37: 103-103. DOI: 10.1200/jco.2019.37.15_suppl.103.
  • Efficacy of immune checkpoint inhibitors (ICI) and genomic characterization of sarcomatoid and/or rhabdoid (S/R) metastatic renal cell carcinoma (mRCC).Bakouny Z, Vokes N, Gao X, Nassar A, Abou Alaiwi S, Flippot R, Bouchard G, Steinharter J, Nuzzo P, Pan W, Flaifel A, Lee G, Braun D, Wei X, Signoretti S, McGregor B, Harshman L, Van Allen E, Choueiri T. Efficacy of immune checkpoint inhibitors (ICI) and genomic characterization of sarcomatoid and/or rhabdoid (S/R) metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2019, 37: 4514-4514. DOI: 10.1200/jco.2019.37.15_suppl.4514.
  • Association of human endogenous retrovirus (hERV) expression with clinical efficacy of PD-1 blockade in metastatic clear cell renal cell carcinoma (mccRCC).Pignon J, Jegede O, Shukla S, Braun D, Horak C, Wind-Rotolo M, Ishii Y, Catalano P, Freeman G, Jennings R, De Cubas A, Rathmell K, Choueiri T, Atkins M, McDermott D, Signoretti S. Association of human endogenous retrovirus (hERV) expression with clinical efficacy of PD-1 blockade in metastatic clear cell renal cell carcinoma (mccRCC). Journal Of Clinical Oncology 2019, 37: 4568-4568. DOI: 10.1200/jco.2019.37.15_suppl.4568.
  • Results of a phase II study of atezolizumab and bevacizumab in non-clear cell renal cell carcinoma (nccRCC) and clear cell renal cell carcinoma with sarcomatoid differentiation (sccRCC).McKay R, McGregor B, Gray K, Steinharter J, Walsh M, Braun D, Flaifel A, VanAllen E, Wei X, Signoretti S, Harshman L, Vaishampayan U, Choueiri T. Results of a phase II study of atezolizumab and bevacizumab in non-clear cell renal cell carcinoma (nccRCC) and clear cell renal cell carcinoma with sarcomatoid differentiation (sccRCC). Journal Of Clinical Oncology 2019, 37: 548-548. DOI: 10.1200/jco.2019.37.7_suppl.548.
  • LBA34 PD-L1 status and clinical outcomes to cabozantinib, sunitinib and everolimus in patients with metastatic clear-cell RCC treated on CABOSUN and METEOR clinical trialsChoueiri T, Flaifel A, Xie W, Braun D, Ficial M, Jennings R, Nassar A, Escudier B, George D, Motzer R, Morris M, Powles T, Wang E, Huang Y, Freeman G, Signoretti S. LBA34 PD-L1 status and clinical outcomes to cabozantinib, sunitinib and everolimus in patients with metastatic clear-cell RCC treated on CABOSUN and METEOR clinical trials Annals Of Oncology 2018, 29: viii726. DOI: 10.1093/annonc/mdy424.040.
  • Optimized management of nivolumab (NIVO) and ipilimumab (IPI) in advanced renal cell carcinoma (OMNIVORE): A response-based phase II study.Wei X, McKay R, Gray K, Stadler W, McDermott D, McGregor B, Agarwal N, Kyriakopoulos C, Carneiro B, Rose T, Zakharia Y, Braun D, Livak K, Wu C, Van Allen E, Signoretti S, Lang J, Hodi F, Choueiri T, Harshman L. Optimized management of nivolumab (NIVO) and ipilimumab (IPI) in advanced renal cell carcinoma (OMNIVORE): A response-based phase II study. Journal Of Clinical Oncology 2018, 36: tps4600-tps4600. DOI: 10.1200/jco.2018.36.15_suppl.tps4600.

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