Debra K. Newman, PhD
Professor, Pharmacology and Toxicology; Senior Investigator at Versiti Blood Research Institute; Adjunct Professor, Microbiology & Immunology
- Versiti Blood Research Institute
Blood Center of Wisconsin
- Blood Platelets
- Platelet Activation
- Platelet Adhesiveness
- Platelet Aggregation
- Platelet Endothelial Cell Adhesion Molecule-1
- Platelet Membrane Glycoproteins
- Protein Interaction Domains and Motifs
- Protein Tyrosine Phosphatases
- Signal Transduction
Platelets are important in early wound healing, where they initially adhere to the extracellular matrix that underlies damaged blood vessels and then aggregate with one another to form a platelet plug. Excessive bleeding occurs when platelet counts are low, or when platelet activity is compromised. Children, especially neonates, who undergo cardiac surgery for repair of congenital heart defects experience excessive bleeding at higher rates than do adults undergoing similar surgeries. We seek to determine the extent to which deficiencies in platelet number or function contribute to excessive bleeding in the setting of pediatric cardiac surgery. This research will help physicians identify pediatric cardiac surgery patients who are at risk for bleeding and administer appropriate blood products in a timely manner should bleeding need to be controlled in this setting.
A major focus of research in our laboratory is Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1). PECAM-1 is an inhibitory molecule that functions in two important contexts. First, PECAM-1 dampens platelet aggregation in response to low levels of stimulation, which is important to prevent pathological thrombosis. Second, PECAM-1 inhibits T cell responses and interferes with the ability of T cells to kill tumors. We have recently discovered that the ability of PECAM-1 to inhibit T cell anti-tumor responses depends on Transforming Growth Factor β (TGFβ), which is another potent T cell suppressor. Our current work is dedicated to development of a better understanding of how PECAM-1 and TGFβ work together to inhibit T cell responses. This research will help us improve T cell-based therapies for treatment of cancer.
(Moroi AJ, Zwifelhofer NM, Riese MJ, Newman DK, Newman PJ.) Blood Adv. 2019 Apr 09;3(7):1154-1166.
(Zwifelhofer NMJ, Bercovitz RS, Weik LA, Moroi A, LaRose S, Newman PJ, Newman DK.) J Thromb Haemost. 2019 Feb;17(2):295-305.
(Newman DK, Fu G, McOlash L, Schauder D, Newman PJ, Cui W, Rao S, Johnson BD, Gershan JA, Riese MJ.) J Leukoc Biol. 2018 11;104(5):883-893.
(Newman DK.) Blood. 2018 09 27;132(13):1359-1360.
(Scott JP, Niebler RA, Stuth EAE, Newman DK, Tweddell JS, Bercovitz RS, Benson DW, Cole R, Simpson PM, Yan K, Woods RK.) World J Pediatr Congenit Heart Surg. 2018 07;9(4):424-433.
(Bercovitz RS, Shewmake AC, Newman DK, Niebler RA, Scott JP, Stuth E, Simpson PM, Yan K, Woods RK.) J Thorac Cardiovasc Surg. 2018 05;155(5):2112-2124.e2.
Diacylglycerol kinase ζ (DGKζ) and Casitas b-lineage proto-oncogene b-deficient mice have similar functional outcomes in T cells but DGKζ-deficient mice have increased T cell activation and tumor clearance.
(Wesley EM, Xin G, McAllister D, Malarkannan S, Newman DK, Dwinell MB, Cui W, Johnson BD, Riese MJ.) Immunohorizons. 2018 Apr 01;2(4):107-118.
(Liao D, Mei H, Hu Y, Newman DK, Newman PJ.) Life Sci. 2018 Jan 15;193:186-193.
(Fu G, Yu M, Chen Y, Zheng Y, Zhu W, Newman DK, Wang D, Wen R.) Eur J Immunol. 2017 01;47(1):74-83.
(Lertkiatmongkol P, Paddock C, Newman DK, Zhu J, Thomas MJ, Newman PJ.) J Biol Chem. 2016 Dec 09;291(50):26216-26225.
(Bercovitz RS, Brenner MK, Newman DK.) Ann Hematol. 2016 Oct;95(11):1887-94.
(Newman DK, Fu G, Adams T, Cui W, Arumugam V, Bluemn T, Riese MJ.) Sci Signal. 2016 Mar 08;9(418):ra27.