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: 

Small molecule protein assembly modulators with pan-cancer therapeutic efficacy.

Open biology

Lingappa AF, Akintunde O, Samueli E, Ewald C, Michon M, Ziari N, Lu M, Yu SF, Froehlich M, Le PU, Fernandez Y, Mallesh S, Lin J, Kitaygorodskyy A, Solas D, Reed JC, Lingappa JR, Müller-Schiffmann A, Korth C, Prasad D, Nalca A, Aston E, Fabbri B, Anand SK, Campi TW, Petrouski E, Dey D, Andrews DW, Rubenstein JL, Lingappa VR

Clinicopathologic features of primary central nervous system anaplastic large cell lymphoma: a multicenter study identifies age and ALK status as prognostic factors.

Journal of hematopathology

Morrow WP, Milligan NS, Ohgami RS, Young KH, Wang B, Vega F, Marques-Piubelli ML, Feldman AL, Slack GW, Savage KJ, Zhao X, Rubenstein JL, Hsi ED

Identification of Genomic Biomarkers of Disease Progression and Survival in Primary CNS Lymphoma.

Blood advances

Geng H, Mo SS, Chen L, Ballapuram A, Tsang M, Lu M, Rauschecker AM, Wen KW, Devine WP, Solomon DA, Rubenstein JL

BTK Degradation As a Novel Therapeutic Strategy in Relapsed CNS Lymphoma: Proof of Concept Studies in Intracranial Patient-Derived, Rodent Models.

Blood

Jun Ma, Michael P Randall, Ming Lu, Lingjing Chen, Huimin Geng, Aishwarya Kumar, Saloni Malla, Mark Noviski, Ryan Rountree, James L. Rubenstein

Toll-like Receptor 7/8 Pathway Is a Therapeutic Target in Primary CNS Lymphoma.

Blood

Michael P Randall, Huimin Geng, Lingjing Chen, Aishwarya Ballapuram, Chitoh Yung, Ming Lu, Gregory Chin, Michael Mish, Jamie Bates, James L. Rubenstein