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K08 Grant Awarded to Deirdre Nolfi-Donegan, MD

March 24, 2022

UPMC Children’s Hospital of Pittsburgh Division of Pediatric Hematology/Oncology congratulates assistant professor of Pediatrics, Deirdre S. Nolfi-Donegan, MD, for receiving a National Institutes of Health (NIH) K08 Mentored Clinical Scientist Research Career Development Award.

Dr. Nolfi-Donegan's NIH grant will fund her research to determine how cell-free hemoglobin released by hemolysis synergizes with high mobility group box 1 protein (HMGB1) to potentiate platelet thrombotic function in sickle cell disease (SCD).  

"I am incredibly excited to have received this grant to further my research into thrombosis formation in sickle cell disease and other hemolytic disorders," says Dr. Nolfi-Donegan. "There are not a lot of translational studies happening in this general area of research, so I am hopeful that we will be able to understand the mechanistic links between hemolysis, inflammation, and thrombosis formation while identifying targets for possible therapeutic development to combat the process."

Dr. Nolfi-Donegan’s translational research will study these mechanistic processes in human samples of hemoglobin and platelets from patients with SCD and healthy controls, and in an animal model of SCD.

The study will attempt to uncover a link between hemolytic and inflammatory processes that contribute to clot formation.

Dr. Nolfi-Donegan’s research is expected to lead to targeted anti-inflammatory and anti-oxidant therapies to treat and prevent SCD-related platelet activation.

“My study is not just looking at sickle cell disease, but rather using sickle cell disease as a broader model for hemolysis and its link to inflammatory pathways that combine to create a pro-thrombotic environment," says Dr. Nolfi-Donegan. “Therefore, our findings in this realm could help us better understand how hemolysis drives thrombosis formation in many other diseases or situations, such as occurs in the setting of thalassemia, paroxysmal nocturnal hemoglobinuria, sepsis, artificial heart valves or mechanical/circulatory support circuits, and others. We know there is an association between hemolysis and the risk of thrombosis, but we do not understand the mechanisms at work. This grant will support my work to better understand this process and provide insights that could be translated into targeted therapies for SCD and other situations in which thrombosis is a significant concern.”

Dr. Nolfi-Donegan is mentored by Cheryl A. Hillery, MD, professor of pediatrics in the Division of Pediatric Hematology/Oncology and director of the Comprehensive Pediatric Sickle Cell Program at UPMC Children’s, and Sruti Shiva, PhD, professor and vice-chair for academics and equity at the University of Pittsburgh Department of Pharmacology and Chemical Biology.  

Read the full abstract of the grant, 1K08HL155488-01A1, at the NIH RePORT website.

Learn more about Dr. Nolfi-Donegan.

Previously published research from Dr. Nolfi-Donegan includes:

Annarapu GK, Nolfi-Donegan D, Reynolds M, Wang Y, Kohut L, Zuckerbraun B, Shiva S. Heme stimulates platelet mitochondrial oxidant production to induce targeted granule secretion. Redox Biol. 2021 Dec 5; 48: 102205. doi: 10.1016/j.redox.2021.102205. Online ahead of print.

Goldenberg M, Shiel M, Subramanian S, Kalpatthi R, Reyes-Múgica M, Nolfi-Donegan D. Splenic kaposiform hemangioendothelioma presenting as insidious consumptive coagulopathy. Am J Hematol. 2021 Dec 1; 96(12): 1708-1714.

Sarangi SN, Gaballah M, Nolfi-Donegan D, Battaglia M, Amin S, Amodio J, Acharya SS. Primary thromboprophylaxis to prevent thrombotic events in pediatric oncology patients with a malignant mediastinal mass. Pediatr Blood Cancer. 2021 Dec; 68(12): e29360.

Annarapu GK, Nolfi-Donegan D, Reynolds M, Wang Y, Shiva S. Mitochondrial reactive oxygen species scavenging attenuates thrombus formation in a murine model of sickle cell disease. J Thromb Haemost. 2021 Sep; 19(9): 2256-2262.

Lapinski J, Nolfi-Donegan D, Cooper JD, Squires RH. Atypical Outcomes for Hepatitis-associated Acquired Aplastic Anemia: 2 Case Studies and Review of the Literature. J Pediatr Hematol Oncol. 2021 Jul 1; 43(5): 195-199. Review.

Nolfi-Donegan D, Braganza A, Shiva S. Mitochondrial electron transport chain: Oxidative Phosphorylation, Oxidant Production, and Methods of Measurement. Redox Biol. 2020 Oct; 37: 101674. Review.

Nolfi-Donegan D, Pradhan-Sundd T, Pritchard KA Jr, Hillery CA. Redox Signaling in Sickle Cell Disease. Curr Opin Physiol. 2019 Jun; 9: 26-33.