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: 

Trial in Progress: A Phase I/II Study of Tafasitamab Plus Lenalidomide in Patients with Relapsed CNS Lymphoma.

Blood

Michael P Randall, Andreas Rauschecker, Liam Gima-Lange, Jenai Wilmoth, Lingjing Chen, Ming Lu, Huimin Geng, Haifaa Abdulhaq, James L. Rubenstein

Molecular profiling identifies at least 3 distinct types of post-transplant lymphoproliferative disorder involving CNS.

Blood advances

Guney E, Lucas CG, Singh K, Pekmezci M, Fernandez-Pol S, Mirchia K, Toland A, Vogel H, Bannykh SI, Schafernak KT, Alexandrescu S, Mobley BC, Powell SZ, Davidson C, Neltner J, Boué DR, Hattab EM, Ferris SP, Ohgami RS, Rubenstein JL, Bollen AW, Tihan T, Perry A, Solomon DA, Wen KW

Older Patients with Primary Central Nervous System Lymphoma: Survival and Prognostication Across 20 US Cancer Centers.

American journal of hematology

David KA, Sundaram S, Kim SH, Vaca R, Lin Y, Singer S, Malecek MK, Carter J, Zayac A, Kim MS, Reddy N, Ney D, Habib A, Strouse C, Graber J, Bachanova V, Salman S, Vendiola JA, Hossain N, Tsang M, Major A, Bond DA, Agrawal P, Mier-Hicks A, Torka P, Rajakumar P, Venugopal P, Berg S, Glantz M, Goldlust SA, Folstad M, Kumar P, Ollila TA, Cai J, Spurgeon S, Sieg A, Cleveland J, Chang J, Epperla N, Karmali R, Naik S, Martin P, Smith SM, Rubenstein J, Kahl B, Evens AM

EBV-positive PCNSL in older patients: incidence, characteristics, tumor pathology, and outcomes across a large multicenter cohort.

Leukemia & lymphoma

Agrawal P, David KA, Chen Z, Sundaram S, Kim SH, Vaca R, Lin Y, Singer S, Malecek MK, Carter J, Zayac A, Kim MS, Reddy N, Ney D, Habib A, Strouse C, Graber J, Bachanova V, Salman S, Vendiola JA, Hossain N, Tsang M, Major A, Gandhi MK, Keane C, Bond DA, Folstad M, Chang J, Mier-Hicks A, Torka P, Rajakumar P, Venugopal P, Berg S, Glantz M, Goldlust SA, Matnani R, Kumar P, Ollila TA, Cai J, Spurgeon SE, Sieg AG, Cleveland J, Epperla N, Karmali R, Naik S, Smith SM, Rubenstein JL, Kahl BS, Chadburn A, Evens AM, Martin P

Stereotactic Radiosurgery for Primary Central Nervous System Lymphoma.

Cureus

Wu SY, Braunstein SE, Rubenstein JL, Sneed PK