Scott A. Peslak

Biography

I am a physician-scientist focused on improving therapeutic approaches for sickle cell disease and beta-thalassemia via study of key signaling pathways that regulate expression of the fetal form of hemoglobin. My graduate work at the University of Rochester School of Medicine focused on the injury and recovery of the red blood cell lineage in a sublethal radiation mouse model (Peslak et al. Exp. Hematol. 2011, Peslak et al. Blood 2012) and was supported by an NIDDK F30 Award. During my Hematology/Oncology fellowship at UPenn as part of the Physician-Scientist Program, I continued my long-standing interest in red cell disorders with a focus on sickle cell disease (SCD) and thalassemia. I joined the lab of Dr. Gerd Blobel in September 2017 to conduct translational research in SCD, specifically studying the role of a recently identified regulator of fetal hemoglobin, heme-regulated inhibitor (HRI). In my postdoctoral work, I found that HRI depletion combined with other pharmacologic inducers of fetal hemoglobin (HbF), including the immunomodulatory drug pomalidomide, leads to clinically significant expression of HbF that significantly reduces sickling in vitro. For this work, I have published a first-author manuscript in Blood Advances (Peslak et al. Blood Adv. 2020) as well as a manuscript in Blood detailing the underlying mechanism of HRI-mediated HbF regulation (Huang, Peslak et al. Blood 2020). To support my research and my current independent laboratory at UPenn, I have been awarded the Doris Duke Charitable Foundation Physician Scientist Fellowship, the UPenn Measey Foundation Physician Scientist Fellowship, an NIDDK K08 Award, and an American Society of Hematology Scholar Award.

I am currently an Assistant Professor of Medicine in the Division of Hematology/Oncology at the University of Pennsylvania Perelman School of Medicine with a clinical focus in adult hematology, particularly SCD and thalassemia. In addition, I am a participating faculty member in the Hematology Research Training Program because I am fully committed to the training of the next generation of physician-scientists. As an independent investigator I plan to delve deeply into the molecular mechanisms of HbF regulation with the central hypothesis that the mechanistic understanding of key cellular signaling pathways underlying hemoglobin switching will lead to innovative, novel SCD therapies. Toward this goal, I carried out a CRISPR-Cas9 based screen to identify additional potentially druggable molecules which might function alone or cooperatively with HRI in governing HbF production. I thus discovered the protein phosphatase PPP6C as a novel HbF regulator. The identification of PPP6C as an HbF regulator forms the basis for my first research direction, which aims to define PPP6C- and HRI-regulated pathways via both hypothesis-driven and unbiased approaches and to investigate suitability of PPP6C and HRI as targets for HbF induction.