Medical Professional Publications

Welcoming New Faculty

A Cluster of New Scientists Join Nationwide Children’s

Hakan Cam, PhD
Center for Childhood Cancer

Cancer is a genetic disorder caused by mutations in genes critically involved in the control of cell proliferation. The p53 family of tumor suppressor genes provides important defense against cancer.  Dr. Cam is focused on the three proteins of the p53 family, p53, p63 and p73, and is using genetic approaches in both cell culture and animal models to understand their roles in tumorigenesis.

He is also using genetic approaches in cell culture and animal models to study mammalian TOR (mTOR) signaling. Several lines of evidence suggest that increased signaling of the mTOR pathway is involved in tumor formation.

Katsumi Kitagawa, PhD
Center for Childhood Cancer

A fundamental requirement of the cell division cycle is the maintenance, replication, and segregation of chromosomal DNA, the specific order of which is ensured by checkpoints.  Dr. Kitagawa is interested in the role that the spindle checkpoint plays in tumor development. Mutations in genes required for kinetochore function and mitotic checkpoint surveillance possibly contribute development of canc

His lab is employing a series of genetic and biochemical strategies to identify additional interacting gene products, regulators, and potential substrates of Sgt1/Skp1/Hsp90 action in yeast and vertebrates. In studies with human cells, Dr. Kitagawa has found a novel mechanism by which 17-AAG (an Hsp90 inhibitor and a novel anti-cancer drug) inhibits cell proliferation and provides the first evidence of HSP90 being required for assembly of kinetochore protein complexes in humans.  Other projects include studying the relationship between mitotic cell death and the spindle checkpoint, and the role of the mitotic cell death in tumorigenesis using mouse models.

Risa Kitagawa, PhD
Center for Childhood Cancer

The spindle assembly checkpoint (SAC) ensures accurate chromosome segregation.  Defects in this system cause chromosome instability that can lead to aneuploidy, a hallmark of many cancers.  Therefore, studies of the genes that regulate SAC activity are directly relevant to research on cancer and many genetic diseases.  Dr. Kitagawa’s research focuses on the characterization of Mad1, a conserved SAC component, and its genetic or physical interactors, using the roundworm C. elegans as a model

Her research addresses the central hypothesis that CeMAD1 is involved in the initial step of the SAC-signaling pathway and that CeMAD1 activity is regulated by multiple pathways that mediate various developmental or environmental cues. Her lab’s goals are to identify and characterize proteins that regulate SAC activity in multicellular organisms and to elucidate the molecular mechanism by which SAC activity is temporally and spatially regulated during development.  She is also investigating a molecular link between DNA damage checkpoint and spindle assembly checkpoint.

Brenda Lilly, PhD
Center for Cardiovascular and Pulmonary Research

Dr. Lilly’s research focuses on understanding the regulatory pathways that control vascular development and smooth muscle differentiation. Using a 3-D culture system to grow blood vessels in vitro, her lab is investigating how smooth muscle precursors are summoned to the nascent vessel. Recruitment of smooth muscle cells is thought to be dependent upon paracrine signals emanating from the endothelial cell tube; however the mechanisms of these signaling events remain a mystery.

Dr. Lilly is also working to define the transcriptional mechanisms that govern selective gene expression in smooth muscle cells. Using smooth muscle regulatory enhancers as tools, her lab directly tests the response that individual components of signaling pathways have on gene expression.

Louise Rodino-Klapac, PhD
Center for Gene Therapy

Dr. Rodino-Klapac’s laboratory is focused on developing gene-therapy-based vectors for the treatment of neuromuscular disorders.  With emphasis on translating laboratory benchside research to the bedside, she is interested in addressing key issues such as transgene delivery, efficacy of gene expression, and immunogenicity, all which have the potential to impact clinical outcomes.

A primary goal is delivering recombinant adeno-associated-virus-mediated vectors by a vascular route to target multiple muscle groups.  One such vector is micro-dystrophin as a potential treatment for Duchenne muscular dystrophy. Gene therapy based therapeutics for other forms of muscular dystrophy, Limb girdle muscular dystrophy type 2D [alpha-sarcoglycan (SGCA) deficiency] and type 2B [dysferlin (DYSF) deficiency are also a key initiative in her lab.  Development of a gene delivery vector for DYSF deficiency using a novel approach with AAV5 is currently underway and future studies will focus on translating these pre-clinical studies to the clinic. 

Christina Valentine, MD, MS, RD
Center for Clinical and Translational Research

Dr. Valentine was previously a neonatology fellow at Nationwide Children’s and now as a principal investigator, she focuses her research on neonatal nutrition. She is studying early neurobiologic development in infants with chronic, life-threatening conditions; effects of early maternal condition and nutrition on infant growth and development.

Her studies have shown that the first 24 hours of life is a crucial time for the administration of nutrition. Preterm infants, when provided amino acids immediately following birth showed significantly improved weight at discharge compared to preterm infants receiving amino acids later in their care. Dr. Valentine has also found that preterm infants receive little docosahexaenoic acid (DHA) during their stay in the neonatal intensive care unit and is investigating supplementing DHA to mothers to prevent prematurity-related outcomes.

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