The Neurological Surgery Department at Wayne State University School of Medicine maintains a multidisciplinary basic and translational research program in neuro-oncology, primarily focused on malignant brain tumors, with emphasis on pre-clinical research aimed at development of novel therapies.

The research program brings together both clinicians and scientists with broad research backgrounds, including neuro-oncology, epilepsy and pain management, cancer biology, chemistry, biochemistry and molecular biology, cell-biology, and immunology. Three research groups are active within the program, each directed by a faculty member of the Neurological Surgery Department - Dr. Sandeep Mittal, M.D., Chief, Neuro-oncology, Dr. Saroj Mathupala, Ph.D., (Biochemistry and Molecular Biology), and Dr. Prahlad Parajuli, Ph.D., (Immunology). The projects undertaken by each group is geared towards discovery or development of novel therapies that can be applicable in a clinical setting against malignant brain tumors.

Brain Tumors - a brief background:

The latest statistics indicate that approximately 41,000 new cases of primary brain tumors will be diagnosed in the United States per year (primary brain tumors form in the brain and tend to stay in the brain). In addition, over 100,000 cancer patients will develop brain tumors due to metastasis of tumors from elsewhere in the body, with breast, lung, and melanoma being the most common cancers to metastasize to the brain. Due to its profound effects on cognition, mobility, personality, and emotion, brain tumors are described as a cancer of the soul (www.tbts.org, www.abta.org).

Of the primary brain tumor cases, approximately 18,000 to 19,000 are diagnosed with malignant brain tumors, or glioblastoma. Being one of the most lethal types of cancers, approximately 15,000 of those diagnosed will tragically die per year, despite interventions with surgery, chemotherapy or radiotherapy.

Brain tumors are now the leading cause of cancer-related deaths in children and young adults under the age 20, surpassing acute lymphoblastic leukemia (ALL). They are also the leading cause of cancer death in male adults aged 20-29 and the fifth largest cancer death among female adults aged 20-39 (www.tbts.org).

GLIOMA BIOENERGETICS RESEARCH GROUP

Saroj P. Mathupala, Ph.D. (Principal Investigator)
Assistant Professor, Neuro-Oncology, Department of Neurological Surgery, Wayne State University School of Medicine
Assistant Professor, Neuro-Oncology, Karmanos Cancer Institute.

E-mail: smathupala@med.wayne.edu
Phone: 313-576-8352
Fax:     313-576-8342

Education and Training:

B.Sc., Chemistry (Hon) University of Colombo, Sri Lanka
Ph.D., Biochemistry and Molecular Biology, Michigan State University, E. Lansing, Michigan (Advisor, Prof. J. Greg Zeikus)
Postdoctoral Fellow, Tumor Bioenergetics and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland (Advisor, Prof. Peter L. Pedersen)

Research Interests By the time many brain tumors are detected, they have been growing silently for years, all the while becoming more aggressive and malignant. Thus, it is generally difficult to treat these tumors. However, such aggressive tumors harbor a few unique biochemical signatures that distinguish them from healthy tissues and organs. Foremost is the tumor’s propensity to abstract excessive quantities of glucose from blood and convert it into lactic acid. This phenomenon of tumor cells is known as the "Warburg Effect," named after its discoverer (Otto Warburg, 1930). In fact, the more malignant the tumor, the greater is its capacity for this abnormal metabolic behavior. It is this feature that is utilized during PET scanning of malignant tumors with radio-labeled glucose analogs.
Thus, this trait of malignant tumors to produce copious amounts of lactic acid can be tested as an "Achilles' Heel" to target and destroy them (while leaving the surrounding healthy brain tissue intact) - the long-term objective of our research group. We are currently exploring the potential of using this as a therapeutic tool against the most malignant of brain tumors, glioblastoma multiforme (GBM)
We are pursuing four major pre-clinical research targets, each geared towards the development of molecular therapeutics against GBMs, or the design of sensitive assays for detection or diagnosis of GBMs.
One of our goals is to identify how the genes that encode proteins responsible for transporting lactic acid out of the tumors (known as monocarboxylate transporters) are regulated in GBMs. The second goal is to identify what enables the GBMs to so rapidly invade the surrounding normal brain tissue in a diffuse manner. Thirdly, we test small-molecule analogs of metabolic precursors as novel drugs that can be harnessed to block lactic acid efflux by GBMs. Another goal is to develop highly sensitive fluorescence based cellular assays for rapid detection and grading of glioma, based on their metabolite signatures.

Former and current students:

The projects are undertaken by both neurosurgery residents (as partial fulfillment of their Ph.D. requirements), and by research associates, medical students/graduate students and undergraduates.

Neurosurgery Residents:
Chaim Colen, M.D.	Ph.D.	(2003-2005)
Todd Francis, M.D.	Ph.D. candidate	(2006-2008)
Medical Students:
Praveen Sateesh	Yr. III Medical Student	(2002 Summer)
Chantel Njiwaji	Yr. III Medical Student	(2004 Summer)
Research Associates and Graduate Students:
Pingyang Yu, M.D.	Research Associate	(2002-2006)
Akannsha Singh, M.B.B.S.	Graduate Student	(2005-2007)
Undergraduate Students:
Noah Heilbrun	Kalamazoo College, MI	(2000 & 2002 Summer)
Scott Gallagher	U. Michigan, MI	(2001 Summer)
Khari Wilson	Grambling St. Univ., LA	(2003 Summer)
Sharon Lu	Yale University, CT	(2003-2004 Summers)
Brandon Koch	Rollins College, FL	(2005-2007 Summers)

Collaborators and consultants:

Dr. Andrew E. Sloan, Associate Professor, Department of Neurological Surgery, Case Western Reserve University Medical School, Cleveland, Ohio.

Dr. Sandeep Mittal, Assistant Professor, Department of Neurological Surgery, and Chief, Neuro-oncology, Karmanos Cancer Institute, Wayne State University School of Medicine.

Research Funding:

American Cancer Society (2000-2002)
LEARN Foundation, Michigan (2002-2006)
Fund for Medical Research and Education (FMRE), Wayne State University School of
Medicine (2004-2006)
Marvin E. Klein, M.D., Charitable Trust (2005-2008)
National Cancer Institute/National Institutes of Health (2006-2011)