James Rubenstein, MD, PhD

Professor In Residence
Department of Medicine
Primary Thematic Area
Cancer Biology & Cell Signaling
Secondary Thematic Area
Immunology
[email protected]
[email protected]

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.

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

Trial in Progress - Alliance A051901 - Phase I Trial of Methotrexate, Rituximab, Lenalidomide, and Nivolumab (Nivo-MR2) Induction Followed By Lenalidomide and Nivolumab Maintenance in Primary Central Nervous System Lymphoma (PCNSL).

Blood

Alvaro J Alencar, Olivia Bobek, Neha Mehta-Shah, Narendranath Epperla, Christine Lu-Emerson, Sarah C. Rutherford, Adam J. Olszewski, Thomas Ollila, Samuel Singer, Travis Dockter, Susan M. Geyer, Lori Rosenstein, Macarena De La Fuente, Eric D. Hsi, Shira N. Dinner, James L. Rubenstein, Nancy L. Bartlett, John P. Leonard

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

Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy.

European journal of human genetics : EJHG

Rudolf G, Lesca G, Mehrjouy MM, Labalme A, Salmi M, Bache I, Bruneau N, Pendziwiat M, Fluss J, de Bellescize J, Scholly J, Møller RS, Craiu D, Tommerup N, Valenti-Hirsch MP, Schluth-Bolard C, Sloan-Béna F, Helbig KL, Weckhuysen S, Edery P, Coulbaut S, Abbas M, Scheffer IE, Tang S, Myers CT, Stamberger H, Carvill GL, Shinde DN, Mefford HC, Neagu E, Huether R, Lu HM, Dica A, Cohen JS, Iliescu C, Pomeran C, Rubenstein J, Helbig I, Sanlaville D, Hirsch E, Szepetowski P

Reply to M.C. Chamberlain.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Rubenstein JL, Cheson BD, Jung SH, Kaplan LD

CNS Lymphoma.

Rare Lymphomas

Agnieszka Korfel, James Rubenstein, German Ott, Eric D. Hsi

Reply to H. Zetterberg et al.

Journal of Clinical Oncology

James L. Rubenstein, Lingjing Chen, Cigall Kadoch, Sushmita Roy, Chris Becker, Howard Schulman

In Reply.

Journal of Clinical Oncology

James Rubenstein, Lauren Abrey, Ranjana Advani, Marc Shuman, Tony Tsai, Joan O'Brien