James Rubenstein, MD, PhD

Professor In Residence
Department of Medicine
Research Overview: 

Our research program addresses three areas in cancer biology and treatment with a focus on brain tumors and their microenvironment.  As a physician-scientist with a background in Hematology/Oncology and in Neuro-Oncology, my group conducts a spectrum of investigations evaluating mechanisms of disease using a variety of approaches including model systems and early phase clinical trials.

Our research focuses on these topics:

1) Brain metastasis: what is the molecular basis for homing of cancer cells to the central nervous system ?

2) Drug resistance within the central nervous system

- How does the cancer microenvironment within the brain suppress the immune response ?

-What are the intrinsic molecular factors that promote drug resistance within the brain tumor microenvironment ?

3) Identification of molecular signals within the cerebrospinal fluid that provide diagnostic, prognostic and mechanistic information regarding brain tumor pathogenesis.

My group led the first effort to study the toxicity, efficacy and immune response of direct injection of anti-lymphoma antibodies into the cerebrospinal fluid in patients with recurrent non-Hodgkin’s lymphoma involving the brain and eyes.  This ongoing line of investigation is facilitating several novel observations regarding the phenotype of drug-resistant lymphoma cells in patients, the interplay between immunotherapy and dynamic changes in macrophage polarization state including differential Fc receptor expression, as well as basic information regarding the cerebrospinal fluid proteome and metabolome in the setting of brain tumors, both at diagnosis and in the relapsed state.

We have developed murine models of brain tumors to address mechanistic questions regarding these three topics.  Methods which we apply include bioluminescence imaging, metabolic imaging, flow-cytometry, and genomics to dissect brain tumor pathobiology.  Our laboratory provides an exceptional opportunity for investigators interested in cancer and in neuroscience, particularly students who wish to gain exposure and training in patient-related research in tumor immunology and drug resistance within the central nervous system.

Primary Thematic Area: 
Cancer Biology & Cell Signaling
Secondary Thematic Area: 
Immunology
Publications: 

A genetically distinct pediatric subtype of primary CNS large B-cell lymphoma is associated with favorable clinical outcome.

Blood advances

Guney E, Lucas CG, Qi Z, Yu J, Zhang R, Ohgami RS, Rubenstein JL, Boué DR, Schafernak KT, Wertheim GB, Dahiya S, Giulino-Roth L, Attarbaschi A, Barth MJ, Kothari S, Abla O, Cohen AL, Mendez JS, Bollen AW, Perry A, Tihan T, Pekmezci M, Solomon DA, Wen KW

Regulation of CNS Lymphoma Progression By the Myeloid Microenvironment.

Blood

Hua-Xin Gao, Eleanor Fraser, Mario Merlini, Huimin Geng, Lingjing Chen, Ming Lu, Yasmin Moshfegh, Joseph Cleveland, Jae Ryu, Jigyasa Sharma, David A. Solomon, Katerina Akassoglou, Clifford Lowell, James L. Rubenstein

Tumor Metabolism and Neurocognition in CNS Lymphoma.

Neuro-oncology

Geng H, Tsang M, Subbaraj L, Cleveland J, Chen L, Lu M, Sharma J, Vigneron DB, Kurhanewicz J, LaFontaine M, Luks T, Barshop BA, Gangoiti J, Villanueva-Meyer JE, Rubenstein JL

A functional mammalian display screen identifies rare antibodies that stimulate NK cell-mediated cytotoxicity.

Proceedings of the National Academy of Sciences of the United States of America

Kang E, Kadoch C, Rubenstein JL, Lanier LL, Wells JA