Research

Our research focus is on developing computational tools for analysis of single-cell RNA sequencing and multimodal data types and applying these tools for improved understanding of tumor immunotherapy resistance mechanisms. With multiple mechanisms of treatment resistance present to varying degreees across tumor types and across patients, it is critical to understand tumor immune interactions within the microenvironment of solid tumors and develop a rational approach to combination therapy in treatment-resistant individuals.

2023

Systematic elucidation and pharmacological targeting of tumor-infiltrating regulatory T cell master regulators

Aleksandar Obradovic, Casey Ager, Mikko Turunen, Thomas Nirschl, Mohsen Khosravi-Maharlooei, Alina Iuga, Christopher M. Jackson, Srinivasan Yegnasubramanian, Lorenzo Tomassoni, Ester Calvo Fernandez, Patrick McCann, Meri Rogava, Angelo M. DeMarzo, Christina M. Kochel, Mohamad Allaf, Trinity Bivalacqua, Michael Lim, Ronald Realubit, Charles Karan, Charles G. Drake, Andrea Califano

Cancer Cell  ·  27 Apr 2023

tumor immunology

Precision immunotherapy

Aleksandar Obradovic

Science  ·  16 Feb 2023

tumor immunology

KLRG1 marks tumor-infiltrating CD4 T cell subsets associated with tumor progression and immunotherapy response

Casey R. Ager, Mingxuan Zhang, Matthew Chaimowitz, Shruti Bansal, Aleksandar Obradovic, Meri Rogava, Johannes C. Melms, Patrick McCann, Catherine Spina, Charles G. Drake, Matthew C. Dallos, Benjamin Izar

Cold Spring Harbor Laboratory  ·  02 Jan 2023

tumor immunology

2022

B7-H3 as a Therapeutic Target in Advanced Prostate Cancer

Christina Guo, Ines Figueiredo, Bora Gurel, Antje Neeb, George Seed, Mateus Crespo, Suzanne Carreira, Jan Rekowski, Lorenzo Buroni, Jon Welti, Denisa Bogdan, Lewis Gallagher, Adam Sharp, Maria D. Fenor de la Maza, Pasquale Rescigno, Daniel Westaby, Khobe Chandran, Ruth Riisnaes, Ana Ferreira, Susana Miranda, Bianca Calì, Andrea Alimonti, Silvia Bressan, Alana H.T. Nguyen, Michael M. Shen, Jessica E. Hawley, Aleksandar Obradovic, Charles G. Drake, Claudia Bertan, Chloe Baker, Nina Tunariu, Wei Yuan, Johann S. de Bono

European Urology  ·  13 Sep 2022

tumor immunology

Immunostimulatory Cancer-Associated Fibroblast Subpopulations Can Predict Immunotherapy Response in Head and Neck Cancer

Aleksandar Obradovic, Diana Graves, Michael Korrer, Yu Wang, Sohini Roy, Abdullah Naveed, Yaomin Xu, Adam Luginbuhl, Joseph Curry, Michael Gibson, Kamran Idrees, Paula Hurley, Peng Jiang, X. Shirley Liu, Ravindra Uppaluri, Charles G. Drake, Andrea Califano, Young J. Kim

Clinical Cancer Research  ·  15 May 2022

tumor immunologysystems biology

Single-Cell RNAseq Analysis Reveals Robust, Anti-PD-1-Mediated Increase of Immune Infiltrate in Metastatic Castration-Sensitive Prostate Cancer

Jessica E. Hawley, Aleksandar Z. Obradovic, Matthew C. Dallos, Emerson A. Lim, Karie Runcie, Casey R. Ager, James McKiernan, Christopher B. Anderson, Joel Decastro, Joshua Weintraub, Renu Virk, Israel Lowy, Jianhua Hu, Matthew G. Chaimowitz, Xinzheng V. Guo, Ya Zhang, Jeremy Worley, Mark N. Stein, Andrea Califano, Charles G. Drake

Cold Spring Harbor Laboratory  ·  09 May 2022

tumor immunologysystems biology

Case Study of Single-cell Protein Activity Based Drug Prediction for Precision Treatment of Cholangiocarcinoma

Aleksandar Obradovic, Lorenzo Tomassoni, Daoqi Yu, Kristina Guillan, Katie Souto, Elise Fraser, Susan Bates, Charles G. Drake, Yvonne Saenger, Filemon Dela Cruz, Andrew Kung, Andrea Califano

Cold Spring Harbor Laboratory  ·  02 Mar 2022

systems biology

Systematic Elucidation and Pharmacological Targeting of Tumor-Infiltrating Regulatory T Cell Master Regulators

Aleksandar Obradovic, Casey Ager, Mikko Turunen, Thomas Nirschl, Mohsen Khosravi-Maharlooei, Christopher Jackson, Vassan Yegnasubramanian, Angelo DeMarzo, Christina Kochel, Mohamad Allaf, Trinity Bivalacqua, Michael Lim, Charles Karan, Charles G. Drake, Andrea Califano

Cold Spring Harbor Laboratory  ·  23 Feb 2022

tumor immunologysystems biology

PISCES: A pipeline for the Systematic, Protein Activity-based Analysis of Single Cell RNA Sequencing Data

Aleksandar Obradovic, Lukas Vlahos, Pasquale Laise, Jeremy Worley, Xiangtian Tan, Alec Wang, Andrea Califano

Cold Spring Harbor Laboratory  ·  25 Jan 2022

systems biology

2021

BCG invokes superior STING ‐mediated innate immune response over radiotherapy in a carcinogen murine model of urothelial cancer

Kara A Lombardo, Aleksandar Obradovic, Alok Kumar Singh, James L Liu, Gregory Joice, Max Kates, William Bishai, David McConkey, Alcides Chaux, Marie‐Lisa Eich, M Katayoon Rezaei, George J Netto, Charles G Drake, Phuoc Tran, Andres Matoso, Trinity J Bivalacqua

The Journal of Pathology  ·  03 Nov 2021

tumor immunology

Integrated analysis toolset for defining and tracking alloreactive T-cell clones after human solid organ and hematopoietic stem cell transplantation

Aleksandar Obradovic, Yufeng Shen, Megan Sykes, Jianing Fu

Software Impacts  ·  02 Oct 2021

transplant immunologysystems biology

Castration-mediated IL-8 promotes myeloid infiltration and prostate cancer progression

Zoila A. Lopez-Bujanda, Michael C. Haffner, Matthew G. Chaimowitz, Nivedita Chowdhury, Nicholas J. Venturini, Radhika A. Patel, Aleksandar Obradovic, Corey S. Hansen, Joanna Jacków, Janielle P. Maynard, Karen S. Sfanos, Cory Abate-Shen, Charles J. Bieberich, Paula J. Hurley, Mark J. Selby, Alan J. Korman, Angela M. Christiano, Angelo M. De Marzo, Charles G. Drake

Nature Cancer  ·  19 Jul 2021

tumor immunology

TGM4: an immunogenic prostate-restricted antigen

Zoila A Lopez-Bujanda, Aleksandar Obradovic, Thomas R Nirschl, Laura Crowley, Rodney Macedo, Alexandros Papachristodoulou, Timothy O’Donnell, Uri Laserson, Jelani C Zarif, Ran Reshef, Tiezheng Yuan, Mithil K Soni, Emmanuel S Antonarakis, Michael C Haffner, H Benjamin Larman, Michael M Shen, Pawel Muranski, Charles G Drake

Journal for ImmunoTherapy of Cancer  ·  30 Jun 2021

tumor immunology

Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages

Aleksandar Obradovic, Nivedita Chowdhury, Scott M. Haake, Casey Ager, Vinson Wang, Lukas Vlahos, Xinzheng V. Guo, David H. Aggen, W. Kimryn Rathmell, Eric Jonasch, Joyce E. Johnson, Marc Roth, Kathryn E. Beckermann, Brian I. Rini, James McKiernan, Andrea Califano, Charles G. Drake

Cell  ·  27 May 2021

tumor immunologysystems biology

Longitudinal Immune Profiling Reveals Unique Myeloid and T-cell Phenotypes Associated with Spontaneous Immunoediting in a Prostate Tumor Model

Casey R. Ager, Aleksandar Z. Obradovic, Juan M. Arriaga, Matthew G. Chaimowitz, Andrea Califano, Cory Abate-Shen, Charles G. Drake

Cancer Immunology Research  ·  01 May 2021

tumor immunology

Lymphohematopoietic graft-versus-host responses promote mixed chimerism in patients receiving intestinal transplantation

Jianing Fu, Julien Zuber, Brittany Shonts, Aleksandar Obradovic, Zicheng Wang, Kristjana Frangaj, Wenzhao Meng, Aaron M. Rosenfeld, Elizabeth E. Waffarn, Peter Liou, Sai-ping Lau, Thomas M. Savage, Suxiao Yang, Kortney Rogers, Nichole M. Danzl, Shilpa Ravella, Prakash Satwani, Alina Iuga, Siu-hong Ho, Adam Griesemer, Yufeng Shen, Eline T. Luning Prak, Mercedes Martinez, Tomoaki Kato, Megan Sykes

Journal of Clinical Investigation  ·  25 Feb 2021

transplant immunology

Blocking IL1 Beta Promotes Tumor Regression and Remodeling of the Myeloid Compartment in a Renal Cell Carcinoma Model: Multidimensional Analyses

David H. Aggen, Casey R. Ager, Aleksandar Z. Obradovic, Nivedita Chowdhury, Ali Ghasemzadeh, Wendy Mao, Matthew G. Chaimowitz, Zoila A. Lopez-Bujanda, Catherine S. Spina, Jessica E. Hawley, Matthew C. Dallos, Cheng Zhang, Vinson Wang, Hu Li, Xinzheng V. Guo, Charles G. Drake

Clinical Cancer Research  ·  19 Jan 2021

tumor immunology

2020

T cell repertoire analysis suggests a prominent bystander response in human cardiac allograft vasculopathy

Marlena V. Habal, April M. I. Miller, Samhita Rao, Sijie Lin, Aleksandar Obradovic, Mohsen Khosravi‐Maharlooei, Sarah B. See, Poulomi Roy, Ronzon Shihab, Siu‐Hong Ho, Charles C. Marboe, Yoshifumi Naka, Koji Takeda, Susan Restaino, Arnold Han, Donna Mancini, Michael Givertz, Joren C. Madsen, Megan Sykes, Linda J. Addonizio, Maryjane A. Farr, Emmanuel Zorn

American Journal of Transplantation  ·  05 Oct 2020

transplant immunology

T-Cell Infiltration and Adaptive Treg Resistance in Response to Androgen Deprivation With or Without Vaccination in Localized Prostate Cancer

Aleksandar Z. Obradovic, Matthew C. Dallos, Marianna L. Zahurak, Alan W. Partin, Edward M. Schaeffer, Ashley E. Ross, Mohamad E. Allaf, Thomas R. Nirschl, David Liu, Carolyn G. Chapman, Tanya O'Neal, Haiyi Cao, Jennifer N. Durham, Gunes Guner, Javier A. Baena-Del Valle, Onur Ertunc, Angelo M. De Marzo, Emmanuel S. Antonarakis, Charles G. Drake

Clinical Cancer Research  ·  01 Jul 2020

tumor immunology

2019

Immunogenicity of prostate cancer is augmented by BET bromodomain inhibition

Wendy Mao, Ali Ghasemzadeh, Zachary T. Freeman, Aleksandar Obradovic, Matthew G. Chaimowitz, Thomas R. Nirschl, Emily McKiernan, Srinivasan Yegnasubramanian, Charles G. Drake

Journal for ImmunoTherapy of Cancer  ·  01 Oct 2019

tumor immunology

Siplizumab selectively depletes effector memory T cells and promotes a relative expansion of alloreactive regulatory T cells in vitro

Manuel A. Podestà, Christian Binder, Felix Sellberg, Susan DeWolf, Brittany Shonts, Siu‐Hong Ho, Aleksandar Obradovic, Elizabeth Waffarn, Nichole Danzl, David Berglund, Megan Sykes

American Journal of Transplantation  ·  18 Jul 2019

transplant immunology

Cross-reactive public TCR sequences undergo positive selection in the human thymic repertoire

Mohsen Khosravi-Maharlooei, Aleksandar Obradovic, Aditya Misra, Keshav Motwani, Markus Holzl, Howard R. Seay, Susan DeWolf, Grace Nauman, Nichole Danzl, Haowei Li, Siu-hong Ho, Robert Winchester, Yufeng Shen, Todd M. Brusko, Megan Sykes

Journal of Clinical Investigation  ·  28 Mar 2019

transplant immunologysystems biology

Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool

Jianing Fu, Julien Zuber, Mercedes Martinez, Brittany Shonts, Aleksandar Obradovic, Hui Wang, Sai-ping Lau, Amy Xia, Elizabeth E. Waffarn, Kristjana Frangaj, Thomas M. Savage, Michael T. Simpson, Suxiao Yang, Xinzheng V. Guo, Michelle Miron, Takashi Senda, Kortney Rogers, Adeeb Rahman, Siu-hong Ho, Yufeng Shen, Adam Griesemer, Donna L. Farber, Tomoaki Kato, Megan Sykes

Cell Stem Cell  ·  07 Feb 2019

transplant immunology

2018

Early expansion of donor-specific Tregs in tolerant kidney transplant recipients

Thomas M. Savage, Brittany A. Shonts, Aleksandar Obradovic, Susan Dewolf, Saiping Lau, Julien Zuber, Michael T. Simpson, Erik Berglund, Jianing Fu, Suxiao Yang, Siu-Hong Ho, Qizhi Tang, Laurence A. Turka, Yufeng Shen, Megan Sykes

JCI Insight  ·  01 Nov 2018

transplant immunology

Quantifying size and diversity of the human T cell alloresponse

Susan DeWolf, Boris Grinshpun, Thomas Savage, Sai Ping Lau, Aleksandar Obradovic, Brittany Shonts, Suxiao Yang, Heather Morris, Julien Zuber, Robert Winchester, Megan Sykes, Yufeng Shen

JCI Insight  ·  09 Aug 2018

transplant immunologysystems biology

2017

Origin of Enriched Regulatory T Cells in Patients Receiving Combined Kidney-Bone Marrow Transplantation to Induce Transplantation Tolerance

B. Sprangers, S. DeWolf, T. M. Savage, T. Morokata, A. Obradovic, S. A. LoCascio, B. Shonts, J. Zuber, S. P. Lau, R. Shah, H. Morris, V. Steshenko, E. Zorn, F. I. Preffer, S. Olek, D. M. Dombkowski, L. A. Turka, R. Colvin, R. Winchester, T. Kawai, M. Sykes

American Journal of Transplantation  ·  01 Mar 2017

transplant immunology

2016

Bidirectional intragraft alloreactivity drives the repopulation of human intestinal allografts and correlates with clinical outcome

Julien Zuber, Brittany Shonts, Sai-Ping Lau, Aleksandar Obradovic, Jianing Fu, Suxiao Yang, Marion Lambert, Shana Coley, Joshua Weiner, Joseph Thome, Susan DeWolf, Donna L. Farber, Yufeng Shen, Sophie Caillat-Zucman, Govind Bhagat, Adam Griesemer, Mercedes Martinez, Tomoaki Kato, Megan Sykes

Science Immunology  ·  01 Oct 2016

transplant immunology