Research Faculty

Address
Irving Cancer Research Center
1130 St. Nicholas Avenue
Rm 202A
New York, NY 10032

Phone: 212-851-4683
Fax: 212-305-7086

td2142@columbia.edu
Affiliations
Pathobiology
Thomas Diacovo, M.D.
Associate Professor in Pediatrics and of Pathology
& Cell Biology

Research Summary

Cell signaling: An area of focus in my lab is to define the role that class I PI3Ks play in the normal and abnormal development of immunocompetent cells. In particular, we have identified specific class I PI3K isoforms that are not only involved in the development and survival of thymocytes but also in T cell Acute Lymphoblastic Leukemia (T-ALL). In collaboration with our colleagues in industry, we have developed novel inhibitors to these PI3K isoforms that not only reduces tumor burden and prolongs survival in mice with T-ALL but also promotes cell death in primary human tumor samples. Work is now focused on the development of a PI3K inhibitor to use in the treatment of T-ALL as well as other hematological malignancy. We are also focused on identifying pathways of resistance through genetic and biochemical screens.

Hemostasis and thrombosis: Another focus of my laboratory is to elucidate mechanisms that promote and platelet interactions with von Willebrand factor (VWF), a plasma protein serves as biological glue, thus permitting platelets to seal off areas vascular damage. Using various genetic, biochemical, structural, and biophysical approaches, we have begun to uncover how naturally occurring genetic mutations in VWF cause bleeding in humans and the role that proteases play in the processing of VWF. Knowledge gained from these studies has enabled my lab to generate genetically altered mice bearing mutations that simulate the bleeding or thrombotic phenotype in these disease states. Moreover, this approach has lead to the development of a mouse model that permits the in vivo study of human platelet behavior at sites of vascular injury that have expedited preclinical screening of antithrombotic therapies for use in patientshh. Work is now focused on the development and testing of new anti-platelet agents.

Selected Publications

1. Boles KS, Vermi W, Facchetti F, Fuchs A, Wilson TJ, Diacovo TG, Cella M, Colonna M. A novel molecular interaction for the adhesion of follicular CD4 T cells to follicular DC. Eur J Immunol. 2009 Mar;39(3):695-703.

2. Randis TM, Diacovo N, Calafat J, Diacovo TG. Shedding light on class I phosphoinositide 3-kinase activity in endothelium. Blood. 2008 May 1;111(9):4827-8; author reply 4828.

3. Randis TM, Puri KD, Zhou H, Diacovo TG. Role of PI3Kdelta and PI3Kgamma in inflammatory arthritis and tissue localization of neutrophils. Eur J Immunol. 2008 May;38(5):1215-24.

4. Chen J, Tan K, Zhou H, Lo HF, Roux DT, Liddington RC, Diacovo TG. Modifying murine von Willebrand factor A1 domain for in vivo assessment of human platelet therapies. Nat Biotechnol. 2008 Jan;26(1):114-9.

5. Zwaginga JJ, Sakariassen KS, King MR, Diacovo TG, Grabowski EF, Nash G, Hoylaerts M, Heemskerk JW. Can blood flow assays help to identify clinically relevant differences in von Willebrand factor functionality in von Willebrand disease types 1-3? J Thromb Haemost. 2007 Dec;5(12):2547-9.

6. Tassi I, Cella M, Gilfillan S, Turnbull I, Diacovo TG, Penninger JM, Colonna M. p110gamma and p110delta phosphoinositide 3-kinase signaling pathways synergize to control development and functions of murine NK cells. Immunity. 2007 Aug;27(2):214-27.

7. Swat W, Montgrain V, Doggett TA, Douangpanya J, Puri K, Vermi W, Diacovo TG. Essential role of PI3Kdelta and PI3Kgamma in thymocyte survival. Blood. 2006 Mar 15;107(6):2415-22.

8. Diacovo TG, Blasius AL, Mak TW, Cella M, Colonna M. Adhesive mechanisms governing interferon-producing cell recruitment into lymph nodes. J Exp Med. 2005 Sep 5;202(5):687-96.

9. Boles KS, Barchet W, Diacovo TG, Cella M, Colonna M. The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8+ T-cell responses through the cell-surface receptor CRTAM. Blood. 2005 Aug 1;106(3):779-86.


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