Biochemistry and Cancer Biology

Current research conducted by faculty members of the Department of Biochemistry and Biology.

MMC and VICC: Partners in eliminating cancer disparities: faculty recruitment
Researcher: Samuel Evans Adunyah, Ph.D.
Funding Source: National Cancer Institute (NCI)
Project Summary: The overall objectives of this project are to strengthen and expand the existing partnership for cancer research between Meharry Medical College (MMC) and the Vanderbilt Ingram Cancer Center (VICC) to achieve three ends: (1) to increase and stabilize the competitive cancer research capability of Meharry; (2) to create stable, long term collaborative relationships between MMC and the VICC in cancer research, research training and career development; (3) to promote, enable and cement a stable, reciprocal, long-term partnership between MMC and VICC based on mutually beneficial research excellence.

MMC and VICC: Partners in eliminating cancer disparities: biobaknking managment program (BMaP) (ARRA)
Researcher: Samuel Evans Adunyah, Ph.D.
Funding Source: National Cancer Institute
Project Summary: The overall objectives of this competing continuation application are to strengthen and expand the existing partnership for cancer research between Meharry Medical College (MMC) and the Vanderbilt Ingram Cancer Center (VICC) to achieve three ends: (1) to increase and stabilize the competitive cancer research capability of MMC; (2) to create stable, long term collaborative relationships between MMC and the VICC in cancer research, research training and career development; (3) to promote, enable and cement a stable, reciprocal, long-term partnership between MMC and VICC based on mutually beneficial research excellence.

The aryl hydrocarbon receptor and breast cancer
Researcher: Sakina Eltom, Ph.D.
Funding Source: National Cancer Institute (NCI)
Project Summary: This study is attempting to define the role AhR plays in invasive breast cancer metastasis, thus establishing it as an independent survival prognostic factor. Studies will also lead to a better understanding of the molecular action of AhR and its ligand-independent activation in advanced breast cancer, thereby providing a unique target for therapeutic interventions.

Improving NK cell adoptive immunotherapy in breast cancer by combinatorial bortezomib and Notch DLL1 treatments
Researcher: Anil Shanker, Ph.D.
Funding Source: National Center for Research Resources (NCRR)/ National Institute on Minority Health and Health Disparities (NIMHD) MeTRC
Project Summary: The body continuously tries to control the appearance of cancer, and cancerous cells continuously try to suppress the body's immune system. This research is attempting to stop tumor cells with a one-two drug punch. One treatment makes the cancer cells easier for the body to kill, and another treatment amps up the body's cancer killing cells.

Mechanisms for B(a)P-induced colon cancer exacerbation by dietary fat
Researcher: Aramandla Ramesh, Ph.D.
Funding Source: National Institute of General Medical Sciences (NIGMS)
Project Summary:This project looks into how environmental toxicants such as benzo(a)pyrene [B(a)P] cause colorectal cancer. It also focuses on how consumption of foods rich in fat accelerates the development of environmentally induced (sporadic) colorectal cancer.

Roles of inflammation-driven chemokines in the pathogenesis of ovarian cancer (SC1)
Researcher: Deok-Soo Son, Ph.D.
Funding Source: National Institute of Allergy/Infectious Diseases (NIAID)
Project Summary: Ovarian cancer is often diagnosed at an advanced stage, after the cancer has spread beyond the ovary, and results in the highest mortality of all cancers of the female reproductive system. Although the precise etiology remains unknown, mounting evidence indicates an impact of inflammation on the development, growth, and progression of ovarian cancer. This project seeks to define the roles of inflammation-driven chemokines in the pathogenesis of ovarian cancer and provide a firm foundation for future long-term survival rates—both for ovarian cancer and other tumors related to inflammation.

Pten-loss dysregulated pathways in prostate cancer
Researcher: Zhenbang Chen, Ph.D.
Funding Source: National Minority Health/Health Disparities (NCMHD)
Project Summary: Prostate Cancer (PCa) is the second leading cause of cancer-related deaths (after lung cancer) in American men, and the morbidity and the mortality to PCa are even higher in African American men as compared Caucasians. The goal of this project is to elucidate Pten-loss dysregulated pathways in prostate cancer (PCa) by defining novel roles of p19Arf in prostate cancer progression including castration resistant prostate cancer (CRPC) growth. Results will provide significant insights into understanding of mechanisms on the incidence and the mortality of PCa, and disparities among ethnic and racial groups.

Mitochondrial homeostasis in anti-tumor T cell-NK cell cross-talk
Researcher: Anil Shanker, Ph.D.
Funding Source: National Cancer Institute (NCI) U54 cancer partnership (MMC, VICC & TSU)
Project Summary: Mitochondrial function is fundamental not only to metabolic homeostasis but also for the formation of immune synapse and lymphocyte activation. This project is investigating mechanisms of mitochondrial dynamics during the functional cross-talk between T lymphocytes and NK cells in an attempt to maximize their anti-tumor activity.

Elucidating binding modes of BRCT-modules
Researcher: Jamaine Davis, Ph.D.
Funding Source: National Cancer Institute (NCI)
Project Summary: There is a fundamental gap in our understanding of how mechanisms of phosphoserine binding modules by BRCT domains enable the assembly of multiprotein DNA repair complexes. Overlooking this gap is an important problem because, until it is solved, understanding how defects in the regulation of DNA repair can potentially cause cancer will remain obscure. The long-term goal is to understand how full-length PTIP regulates the DNA damage response pathway. The objective of this particular application is to provide a molecular description of how PTIP-(BRCT)4 interactions help to regulate DNA repair.

Inflammatory bowel disease and colorectal malignancy
Researcher: Amosy E. M'Koma, M.D., Ph.D.
Funding source: U54 cancer partnership grant (MMC-VICC)
Project Summary: This research specializes in inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's colitis (CC), indeterminate colitis (IC) and associated colorectal carcinogenesis. Its particular specialty is diagnostic methodologies, specifically as they relate to the biopathophysiology of IBD. The research efforts are directed towards developing strategic methodologies to identify proteomic patterns that are (i) IBD phenotype delineator and (ii) oncogenic. Researchers use MALDI MS technology to mining human colon mucosal and sub-mucosal layers to analyze proteins of interest. The proteins that are primarily found in the mucosa would be amenable to proteomic interrogation from endoscopic biopsies and those in the sub-mucosa would have the potential to become amenable to proteomic studies in the serum as biomarker(s). These proteins may provide a powerful screening tool in early pre-neoplastic detection in histologically normal epithelium as well as delineation of IBD by non-invasive, easier, affordable, accurate and faster screening. An accurate diagnosis is of paramount importance in terms of evidenced personalized medical therapy, surgical intervention and prognosis.

Notch ligands in regulation of anti-cancer immunity
Funding Source: National Cancer Institute (NCI) R01 subcontract
Researcher: Anil Shanker, Ph.D.
Project Summary: Adequate Notch signaling in the immune compartment is critical for the induction of anti-tumor immunity. In this project, in collaboration with Drs. David Carbone and Mikhail Dikov at Ohio State University, the team focuses to achieve a molecular understanding of the roles of Notch, DLL1 and other Notch ligands in anti-tumor T cell immunity. They are also evaluating the therapeutic and prognostic potential that Notch system could offer to enable the translation into clinically relevant cancer therapeutics and prognostic assays.

Differentiating Ulcerative Colitis and Crohns Colitis Through Proteomic Patterns
Researcher: Amosy E. M'Koma, M.D., Ph.D.
Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Project Summary: Researchers in Dr. M'Koma's lab anticipate identifying novel molecular biometric fingerprints that will allow delineation of inflammatory bowel disease called ulcerative colitis (UC) and Crohn's colitis (CC) as well as potentially predict indeterminate colitis (IC) eventual differentiation into either UC or CC. They hypothesize that these biological signature candidates that distinguish UC from CC and normals represent identifiable proteins that are able to be sequenced and identified.

Defining the effects of bortezomib on NK cell activation in cancer
Funding Source: National Cancer Institute (NCI) SCORE SC1
Researcher: Anil Shanker, Ph.D.
Project Summary: Work in a tumor model demonstrated that along with CD8 T cells, NK cells are indispensable for complete tumor regression, by preventing the development of antigen-deficient tumor escape variants. The major goal of this project is to define the effects of cell-death-sensitizing anti-cancer drug bortezomib on tumor microenvironment and NK cell function in mouse models of cancer.

Eastern Cooperative Oncology Group Clinical Trial (E6508) Laboratory Study: Fraction of immature myeloid cells and dendritic cells
Researcher: Anil Shanker, Ph.D.
Funding Source: Frontier Science & Technology Research Foundation, Inc., EMD Serono, Inc.
Project Summary: Expansion of immunosuppressive immature myeloid cells and inadequate function of dendritic cells is one mechanism of tumor escape from immune system control that may compromise the efficacy of cancer immunotherapy. The goal of this study is to determine the fraction of circulating dendritic cells and immature myeloid cells in blood samples as the prognostic markers of anti-tumor immune status in radiation-treated stage III non-squamous NSCLC lung cancer patients before, during, and after administration with Mucin-1 liposome vaccine (L-BLP25) and the anti-VEGF antibody (bevacizumab).