Department of Molecular and Cellular Biochemistry 

Michael Ostrowski, PhD, Chair

Research in the Department of Molecular and Cellular Biochemistry advances basic understanding of the biochemical and molecular mechanisms underlying both normal cellular processes and disease states in humans. Through multidisciplinary collaborative work, scientists can translate these basic findings into studies that will benefit patients. This research focus is exemplified by two translational National Cancer Institute program project grants for which Department faculty members serve as principal investigators. These projects include faculty members in both clinical and basic science departments across the Medical Center. In addition, all faculty in the Department of Molecular and Cellular Biochemistry are associated with Medical Center Signature Programs, including cancer, heart and neurosciences – representing the highest level of faculty participation in these programs within the School of Biomedical Sciences.

Ongoing Research Programs

• Genetic and epigenetic mechanisms governing the transcriptional regulation of gene expression
• Molecular mechanisms underlying neuromuscular diseases
• Molecular genetics of the regulation of RNA processing, transport and stability
• Structural biology of homologous recombination and cytokine signaling
• Molecular and cell biology of cardiovascular disease

Research Accomplishments of 2006

• Samson Jacob, PhD, leads a multidisciplinary team that received a five-year, $12 million program project grant from the National Cancer Institute to study basic mechanisms and translational applications of epigenetic modifications of DNA and chromatin in human leukemia. The project team includes Department faculty members Mark Parthun, PhD, and Saïd Sif, PhD. This team covers all aspects of epigenetic modifications, including DNA methylation, histone modification and chromatin remodeling.
• Tsonwin Hai, PhD, participated in a collaborative study that used a systems biology approach to identify an unexpected role for the transcription factor ATF-4 in innate immunity (Nature 441:173- 178). Hai discovered ATF-4 in 1989 and has used a variety of approaches, including mouse genetic models, to study the role of this stress-activated transcription factor in several biological processes, including diabetes. In this study, her mouse genetic model demonstrated that ATF-4 can also repress expression of proinflammatory genes in immune cells, a necessary step for a normal immune response. This work implicates ATF-4 as an important factor to study in inflammatory diseases, including rheumatoid arthritis and cancer.
• Dan Schoenberg, PhD, director of the campuswide RNA Group, was on a team of Ohio State investigators that identified a novel mechanism that retroviruses use to increase translation of viral genes. The virus uses a unique RNA structure to recruit a cellular protein, RNA helicase A, to increase translation of viral RNA to protein. This group found that the same RNA structural element is found in many cellular RNAs, and that RNA helicase A can also increase translation of these cellular RNAs, including RNA that encode for genes involved in cancer cell growth. The work may help improve the design of vectors for gene therapy and enhance understanding of how genes are aberrantly expressed in cancer cells.
• Kamal Mehta, PhD, and his group made the unexpected finding that the small molecule inhibitor of the JNK family of stress-inducible kinases, SP600125, can also inhibit phosphorylation of histone 3 at position ser10 (H2Ser10). Through studies with this compound, researchers discovered that the low-density lipoprotein receptor, involved in transporting cholesterol across cell membranes, is negatively regulated by histone H3-Ser10 phosphorylation. These studies will guide development of more effective agents for treating hypercholesterolemia and cancer.
• Charles Bell, PhD, led a study that used NMR spectroscopy and X-ray crystallography to determine the three-dimensional structure of PF1378 (Pfu Pop5), one of four protein subunits of archaeal RNase P that shares a homolog in the eukaryotic enzyme. RNase P is a ubiquitous and essential enzyme in all domains of life. It is responsible for cleaving the single-stranded 5’ leader sequence of precursor tRNA, a vital reaction in the maturation of tRNA. With the elucidation of the Pfu Pop5 structure, a functional role for the protein can be hypothesized. These data provide clues about the role of Pop5 in the archaeal and eukaryotic RNase P enzymes and will lend insight into the structural and functional connections between the three domains of life of this conserved yet compositionally variable enzyme.