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J. Yasha Kresh, Ph.D.
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Professor, School of Biomedical Engineering, Science & Health Systems
Office: 6320 Ncb Email: jkresh@drexelmed.edu
Phone: 215.762.1703 Fax: 215.762.5021
Personal Web Page: Click Here to Visit Personal Web Page
Research Keywords:
Cardiac Repair and Regeneration, Tissue Engineering, Cardiovascular System Dynamics, Systems Biology, Cellular Networks, Cardiovascular Engineering, Tele-robotics
Education:
Rutgers University, Biomedical Engineering/ Cardiovascular Physiology
1977
Active Research Projects:
Learning and scholarly interaction are fostered in an atmosphere of discovery within the Cardiothoracic Research and Cardiovascular Biophysics Laboratory, which is an interdisciplinary core facility bridging the Department of Cardiothoracic Surgery and the Division of Cardiovascular Diseases at DU College of Medicine. The research projects draw on a large multidisciplinary knowledge base, applying the thinking, phenomena, techniques, and technology of cardiovascular engineering, cellular and tissue engineering, biophysics, mathematical/computational biology and systems theory to the solution of basic and clinical cardiovascular problems. The broad range of research projects that been pursued reflects this unique interdisciplinary approach. Importantly, this facility also serves as an educational cardiac research center to direct the scientific projects of medical and surgical residents, as well as graduate and medical students. In addition, the collaborative efforts include projects with the Tissue Engineering and Robotic Surgery groups at Drexel University.
The CT-Surgery Lab is a multi-faceted research facility, currently supporting the activity of two Bioengineering graduate students and one Post Doctoral Research Fellow. Our research portfolio consists of:
1. A comprehensive program focused on the surgical management of end stage heart failure (AHA, DOD, C-PA Tobacco, Industrial support).
This overarching effort includes investigation of:
a. Topobiology of cellular cardiomyoplasty (milieu-dependent cardiomyocyte differentiation and adaptation)
b. In vitro "pre-programming" of adult stem cells (hMSC commitment, differentiation)
c. Molecular imaging and assessment of remodeled human hearts (role of MMP-3 and TIMP-1)
d. Effects of temporary ventricular support devices on cellular and biochemical markers of left ventricular reverse-remodeling
e. Long-term cardiac and pulmonary functional substitution with artificial devices and electrically active polymer muscle constructs.
2. Efforts to improve the capabilities of robot-assisted cardiac surgery, through the incorporation of sensors that provide haptic (tactile) feedback to the user, and through improvements in computer imaging and vision.
3. Tele-linked collaborative research programs focused on cellular interactions using a unique, custom-designed live-cell observatory. This allows multiple researchers to view and interact with cell cultures from remote distances in real time.
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“Homing Stem Cells for Cardiac Repair”
When a blockage of the coronary artery occurs, cardiomyocytes become injured. This injury induces the release a variety of cytokines as well as chemokines into the circulation. Chemokines play a pivotal role in "pulling" endothelial progenitor cells from the bone marrow and directing them to areas of injury. We hypothesize that the injured cardiac cells serve as the signaling nidus, initiating the chemokine mediated chemotactic gradient; acting as a local homing signal directing these stem cells towards the infracted area.
The experimental protocols are designed to establish the presence and quantify the cytokines/chemokines in peripheral circulation in response to myocardial injury, and evaluate the corresponding numbers of stem cell in circulation. This information will benefit the growing field of cell-based therapy that is attempting to repair and restore the injured myocardium. This may provide a means by which autologus progenitor cells can be chemically guided to both prevent the progression of myocyte injury following infarction, as well as, a potential therapy for treating end stage heart failure. The identification and quantification of both cytokines and chemokines, may aid in the development of a new marker for myocyte injury, leading to new screening tools for the early diagnosis of myocardial infarction. In addition the knowledge gained by understanding the process by which endogenous stem cells home to an area of injury will allow for the development of new therapies for guiding the healing process not only in the heart, but in other organ systems as well.
Publications:
B. Selected peer-reviewed publications (Selected from 170).
1: Min BG, Kresh JM, Fich S, Kostis JB, Welkowitz W. Relation between computed zero-load aortic flow and cardiac muscle mechanics. J Biomech. 1978;11(5):227-35.
2: Kresh JY, Brockman SK. Left ventricular volume modulation - analysis of assisted circulation.
Trans Am Soc Artif Intern Organs. 1982;28:110-6.
3: Kresh JY, Brockman SK.An interactive microcomputer-based graphics system for analysis of cardiodynamic function. Comput Biol Med. 1984;14(4):419-27.
4: Kresh JY, Cobanoglu MA, Brockman SK. The intramyocardial pressure: a parameter of heart contractility.
J Heart Transplant. 1985 Feb;4(2):241-6.
5: Kresh JY, Brockman SK.Catecholamine effects during and after cardiopulmonary bypass.
J Thorac Cardiovasc Surg. 1985 Apr;89(4):655-7.
6: Kresh JY, Brockman SK.A model-based system for assessing ventricular chamber pressure-volume-dimension relationship: regional and global deformation. Ann Biomed Eng. 1986;14(1):15-33.
7: Kresh JY, Kerkhof PL, Goldman SM, Brockman SK.heart-mechanical assist device interaction.
ASAIO Trans. 1986 Jul-Sep;32(1):437-43.
8: Kresh JY, Nastala C, Bianchi PC, Goldman SM, Brockman SK. The relative buffering power of cardioplegic solutions.
J Thorac Cardiovasc Surg. 1987 Feb;93(2):309-11.
9: Kresh JY, Brockman SK. Autoperfusing ectothermic heart-lung preservation system.
J Invest Surg. 1989;2(3):281-91.
10: Rabbany SY, Kresh JY, Noordergraaf A. Intramyocardial pressure: interaction of myocardial fluid pressure and fiber stress. Am J Physiol. 1989 Aug;257(2 Pt 2):H357-64.
11: Chandrasekaran K, Ross J Jr, Covalesky VA, Kresh JY, Mintz GS. Two-dimensional echocardiographic visualization of turbulent intracardiac blood flow across the stenotic mitral valve. Am Heart J. 1989 Sep;118(3):625-7.
12: Kresh JY, Fox M, Brockman SK, Noordergraaf A. Model-based analysis of transmural vessel impedance and myocardial circulation dynamics. Am J Physiol. 1990 Jan;258(1 Pt 2):H262-76.
13: Kresh JY, Brockman SK, Noordergraaf A. Theoretical and experimental analysis of right ventricular bypass and univentricular circulatory support. IEEE Trans Biomed Eng. 1990 Feb;37(2):121-7.
14: Kresh JY. Myocardial modulation of coronary circulation. Am J Physiol. 1990 Dec;259(6 Pt 2):H1934-7.
15: Kresh JY. Myocardial mechanics and energetics revisited. ASAIO Trans. 1991 Oct-Dec;37(4):537-9.
16: Kresh JY. Intramyocardial mechanical states: vessel-interstitium-muscle interface.
Adv Exp Med Biol. 1993;346:113-23.
17: Frasch HF, Kresh JY, Noordergraaf A. Wave transmission and input impedance of a model of skeletal muscle icrovasculature. Ann Biomed Eng. 1994 Jan-Feb;22(1):45-57.
18: Izrailtyan I, Frasch HF, Kresh JY. Effects of venous pressure on coronary circulation and intramyocardial fluid mechanics. Am J Physiol. 1994 Sep;267(3 Pt 2):H1002-9.
19: Frasch HF, Kresh JY, Noordergraaf A. Two-port analysis of microcirculation: an extension of windkessel.
Am J Physiol. 1996 Jan;270(1 Pt 2):H376-85.
20: Skinner JE, Wolf SG, Kresh JY, Izrailtyan I, Armour JA, Huang MH. Application of chaos theory to a model biological system: evidence of self-organization in the intrinsic cardiac nervous system.
Integr Physiol Behav Sci. 1996 Apr-Jun;31(2):122-46.
21: Morris RJ, Strong MD, Grunewald KE, Kuretu ML, Samuels LE, Kresh JY, Brockman SK. Internal thoracic artery for coronary artery grafting in octogenarians. Ann Thorac Surg. 1996 Jul;62(1):16-22.
22: Izrailtyan I, Kresh JY.Bradykinin modulation of isolated rabbit heart function is mediated by intrinsic cardiac neurons. Cardiovasc Res. 1997 Mar;33(3):641-9.
23: Rabbany SY, Kresh JY, Noordergraaf A. Differentiation of intramyocardial fluid pressure from fiber stress.
Technol Health Care. 1997 Apr;5(1-2):145-57
24: Kresh JY, Armour JA. The heart as a self-regulating system: integration of homeodynamic mechanisms.
Technol Health Care. 1997 Apr;5(1-2):159-69.
25: Kresh JY, Izrailtyan I. Evolution in functional complexity of heart rate dynamics: a measure of cardiac allograft adaptability. Am J Physiol. 1998 Sep;275(3 Pt 2):R720-7.
26: Kresh JY, Izrailtyan I, Morris RJ, Wechsler AS. Vascular determinants of univentricular support.
ASAIO J. 1998 Sep-Oct;44(5):M330-5.
27: Kresh JY, Wechsler AS. Heart reduction surgery can reconstitute the residual stress-strain state of the left ventricle. J Thorac Cardiovasc Surg. 1998 Dec;116(6):1084-6.
28: Izrailtyan I, Kresh JY, Morris RJ, Brozena SC, Kutalek SP, Wechsler AS. Early detection of acute allograft rejection by linear and nonlinear analysis of heart rate variability.J Thorac Cardiovasc Surg. 2000 Oct;120(4):737-45.
29. Noronha, V., Yarman, C.E., Kresh, J.Y., Onaral, B. “A Remote Monitoring of Cellular Network Assembly and Function”, Proceedings, 23rd Annual International Conference on the IEEE Engineering in Medicine and Biology Society, pp 142- October, 2001
30. Kennedy, C.W., Hu, T., Desai, J.P., Wechsler, A. S., Kresh, J.Y. "A Novel approach to Robotic Cardiac Surgery Using Haptics and Vision", Cardiovascular Engineering: An International Journal, Vol. 2 No. 1:15-22 , 2002.
31. Kerkhof, P.L.M., Li, J.K-J., Kresh, J.Y. ”An Analytical Expression for the Regulation of Ventricular Volume in the Normal and Diseased Heart”, Cardiovascular Engineering: An International Journal, Vol. 2 No. 2: 37-48, 2002.
32. Rangappa, S., Entwistle J.W., Wechsler, A.S., Kresh, J.Y “Cardiomyocyte-Mediated Contact Programs Human Mesenchymal Stem Cells to Express Cardiogenic Phenotype” Journal of Thoracic and Cardiovascular Surgery, Vol 126:124-132, 2003.
33. Deisboeck, T.S., Kresh J.Y., (eds): Complex Systems Science in BioMedicine. Kluwer Academic/Plenum Publishers, New York, NY, USA. (In Press)
34. Bolno, P.B., Kresh, J.Y., “Physiologic and Hemodynamic Basis of Ventricular Assist Devices” Cardiology Clinics Vol. 21, 15-27, 2003.
Patents:
Pacing System and Method for Cardiac Pacing As a Function of Determined Myocardial Contractility:
U.S. Patent # 4,936,304
Myocardial Contractility-Sensitive Pacer: French and German Patents # 0244446 / 3673643
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