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: 

Cutaneous T cell lymphoma PDX drug screening platform identifies cooperation between inhibitions of PI3Ka/d and HDAC.

The Journal of investigative dermatology

Wu CH, Yang CY, Wang L, Gao HX, Rakhshandehroo T, Afghani S, Pincus L, Balassanian R, Rubenstein J, Gill R, Bandyopadhyay S, McCormick F, Moasser M, Ai WZ

On Point in Primary CNS Lymphoma.

Hematological Oncology

Tsang M, Cleveland J, Rubenstein JL

Myeloablative versus non-myeloablative consolidative chemotherapy for newly diagnosed primary central nervous system lymphoma: Results of induction therapy in Alliance 51101.

Journal of Clinical Oncology

Tracy Batchelor, Sharmila Giri, Amy S. Ruppert, Nancy L. Bartlett, Eric D. Hsi, Bruce D. Cheson, Lakshmi Nayak, John Paul Leonard, James L. Rubenstein

THERAPEUTIC VITRECTOMY AS AN ADJUNCT TREATMENT TO SYSTEMIC CHEMOTHERAPY FOR INTRAOCULAR LYMPHOMA.

Retinal cases & brief reports

Bever GJ, Kim DJ, Afshar AR, Rubenstein JL, Damato BE

Potential Genetic and Immunologic Mechanisms of Therapeutic Resistance and Disease Progression in CNS Lymphoma Elucidated Via Whole Brain Autopsy Studies.

Blood

David A. Solomon, Huimin Geng, Raymond A. Sobel, Lakshmi Subbaraj, Mazie Tsang, James L. Rubenstein