About Us : Research Scientists

Scott M. Welford, Ph.D.

Biography:

Dr. Welford has expertise in molecular biology, radiation oncology, and animal models of cancer, and focuses his research efforts towards developing novel strategies to combat cancer. Dr. Welford completed his doctoral studies at the Molecular Biology Institute of UCLA, under the supervision of Dr. Chris Denny, where his work investigated the molecular mechanisms of the chimeric transcription factors associated with Ewing’s Sarcoma. Ewing’s Sarcoma is genetically defined by recurrent chromosomal translocations that produce chimeric transcription factors. The fusion of principally an RNA binding protein (EWS) to the DNA binding domains of one of three predominant ETS transcription factors (FLI1, ERG, or ETV1) results in the aberrant expression of cohorts of target genes. A major question in the Ewing’s field was to define relevant target genes with altered expression to gain insight into how EWS/ETS fusions could drive tumorigenesis. Through the progress of this PhD work, Dr. Welford developed novel and highly impactful technologies to integrate microarray based transcriptional profiling with subtractive hybridization techniques, and elucidated mechanisms at work in Ewing’s Sarcoma.

Subsequently, Dr. Welford joined the laboratory of Dr. Amato Giaccia in the Department of Radiation Oncology at Stanford University for post-doctoral studies. The primary focus while at Stanford was in understanding the how aspects of tissue microenvironments contribute to tumor development and evolution. Hypoxia is a characteristic of nearly all solid tumors, developing as a result of limited blood supply to tumors and improper and inefficient angiogenesis. Dr. Welford’s studies were among the first to investigate the effects normal tissue oxygenation, which can range to levels that are quite low, on the transformation potential of common oncogenes. He showed that hypoxia, through HIF1, drives expression of a secreted cytokine (MIF) that could suppress the senescent effects of oxidative stress, arguing that in vivo oxygenation can serve as a protected niche for the early steps of cellular transformation. In kidney cancer, the defining genetic alteration is inactivation of the VHL tumor suppressor. Others had shown that loss of VHL could induce senescence in vitro. Dr. Welford then went on to demonstrate that oxygenation found in the kidney cortex could suppress VHL-loss induced senescence in vitro and in vivo, providing a possible explanation for the tissue specificity of VHL associated tumors. Together, the studies provided background for the current hypothesis that hypoxic niches serve as protective environments in tissues for cells that can reconstitute tumors.

Dr. Welford then moved to be independent investigator in Radiation Oncology at Case Western Reserve University as an Assistant Professor and eventually as an Associate Professor with tenure where his projects utilized basic tissue culture models, animal tumor models, and clinical trial samples to more clearly define unique aspects of tumor cells that can be used for therapeutic intervention. During this time, the research interests expanded to microenvironmental adaptations that promote resistance to ionizing radiation. Currently, Dr. Welford has joined the University of Miami as an Associate Professor to continue his research program. Together, the efforts support his overarching goals of identifying tumor determinants of therapeutic resistance, and devising strategies for sensitization.