BCM Department of Medicine
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Thrombosis Research Section Faculty

 

Faculty (Secondary Appointment)

MICHAEL KROLL, M.D.

 

 

 

 

Research Interests:

Dr. Kroll’s research is involved in three general areas. The first is to elucidate molecular mechanisms of platelet activation triggered by shear-induced von Willebrand factor (VWF) binding to the glycoprotein Ib-IX-V complex. He is particularly focused on the role of tyrosine kinases and phosphatidylinositol 3-kinase in this process, and the mechanisms by which they are activated. The second area of work is in drug development. Dr. Kroll hopes to identify critically important molecular interactions that drive platelet thrombosis under conditions of pathological shear stress, and screen for small molecules that inhibit them in cell-free systems, intact human platelets in vitro, and in animal models. Dr. Kroll’s third area of research is to develop technology for generating mutant human platelets through the genetic engineering of human stem cells maturing into megakaryocytes ex vivo. He would like to use this system to study the first two areas described above, and his hope is to someday develop novel cell therapies.

 

Selected Publications:

1. Reséndiz JC, Feng S, Ji G, Francis KA, Berndt MC, Kroll MH. Purinergic P2Y receptor blockade inhibits shear-induced platelet phosphatidylinositol 3-kinase activation. Molecular Pharmacology 2003; 63:639-645.

2. Feng S, Reséndiz JC, Christodoulides N, Lu X, Arboleda D, Berndt MC, Kroll MH. Pathological shear stress stimulates the tyrosine phosphorylation of a-actinin associated with the GpIb-IX complex. Biochemistry 2002;41:1100-1108.

3. Christodoulides N, Feng, S, Resendiz JC, Berndt MC, Kroll MH. Glycoprotein Ib/IX/V binding to the membrane skeleton maintains shear-induced platelets aggregation. Thrombosis Research 2001;102: 133-142.

4. Feng, S, Christodoulides N, Resendiz J, Berndt MC, Kroll MH. Regulation of 14-3-3 protein binding to GpIb/V/IX by the cytoplasmic domains of GpIba and GpIbb. Blood 2000;95:550-557.

5. Feng, S, Christodoulides N, Kroll MH. The glycoprotein Ib complex regulates cell proliferation. Blood 1999;93:4256-4263.

6. Kroll MH, Hellums JD, McIntire LV, Schafer AI, Moake JL. Platelets and shear stress. Blood 1996;88:1525-1541.

7. Razdan K, Hellums JD, Kroll MH. Shear stress-induced von Willebrand factor binding to platelets causes the activation of tyrosine kinase(s). Biochemical Journal 1994;302:681-686.

8. Kroll MH, Hellums JD, Guo Z, Durante W, Razdan K, Hrbolich JK, Schafer AI. Protein kinase C is activated in platelets subjected to pathological shear stress. J Biol Chem 1993;268:3520-3524.

9. Chow TW, Hellums JD, Moake JL, Kroll MH. Shear stress induced von Willebrand factor binding to platelet glycoprotein Ib initiates calcium influx associated with aggregation. Blood 1992;80:113-120.

10. Kroll MH, Harris TS, Moake JL, Handin RI, Schafer AI. von Willebrand factor binding to platelet glycoprotein Ib initiates signals for platelet activation. J Clin Invest 1991;88:1568-1573.


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