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Thrombosis Research Section Faculty
Faculty (Secondary Appointment)
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.
©1995-2003
Baylor College of Medicine
Email: medicine@bcm.tmc.edu
URL: http://public.bcm.tmc.edu/medicine/kroll.html (Modified:
June 3, 2003
)
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