Indiana University School of Medicine

Loren J. Field, PhD

Loren J. Field, Ph.D.
Professor of Medicine and Pediatrics

Association

Department of Pediatrics
Indiana University School of Medicine

Contact

317-274-5085 office
317-274-2007 lab
317-278-9298 fax

Education
  • Postdoctoral Fellowship: Molecular Biology, Roswell Park Memorial Institute, Buffalo, New York
  • Ph.D.: Cell & Molecular Biology (1982), State University of New York at Buffalo
  • M.S.: Cell & Molecular Biology (1980), State University of New York at Buffalo
  • B.A.: Biology (cum laude) (1978), State University of New York at Oswego
Academic and Professional
Roles and Appointments: Current
Academic and Professional
Roles and Appointments: Past
  • Visiting Scientist (1986 - 1987), Staff Investigator (1987 - 1989), Senior Staff Investigator (1989 - 1990), Cold Spring Harbor Laboratory, Cold Spring, NY
Awards, Honors and Distinguished
Professional Activities
  • Associate Editor: Cardiovascular Research, Molecular Therapy
  • Editorial Boards: Circulation, Circulation Research, Regenerative Medicine, Cloning and Stem Cells, Journal of Molecular and Cellular Cardiology, Cardiovascular Research, Heart Rhythm, Molecular Therapy, Organogenesis, Netherlands Heart Journal
  • Elected Founding Fellow, International Society of Heart Research (2001)
  • Recipient of the Bristol Myers Squibb Unrestricted Grant Award (1996-2000)
  • American Heart Association, Established Investigator
  • Recipient, Glenn W. Irwin, Jr., M.D. Research Scholar Award, IUPUI (2012)
Research Interest

Although the adult mammalian heart retains some capacity for cardiomyocyte renewal (resulting from cardiomyocyte proliferation and/or cardiomyogenic stem cell activity), the magnitude of this regenerative process is insufficient to effect repair of substantively damaged hearts. My lab has a long standing interest in developing strategies to induce regenerative growth, and developing strategies to promote cardioprotection. We have focused on two approaches to promote regenerative growth. The first entails inducing proliferation in surviving cardiomyocytes following myocardial injury. Towards that end we have identified a number of gene products which, when expressed in cardiomyocytes, induce proliferation. For example, we have demonstrated that targeted expression of the G1/S regulatory protein cyclin D2 results in a 50% reduction in infarct size and a concomitant 90% recovery in cardiac function within 180 days following permanent coronary artery occlusion. Our current efforts in studying cardiomyocyte cell cycle regulation are focused on understanding how differential post-translational regulation of the endogenous D-type cyclins limits the proliferative potential of adult cardiomyocytes. The second approach to promote regenerative growth focuses on the transplantation of cardiomyocytes or cardiomyogenic stem cells into the damaged myocardium. For example, we have shown that both fetal and embryonic stem cell-derived cardiomyocytes are able to structurally integrate into the adult myocardium, and are able to participate in a functional syncytium with the host heart. Our current efforts are focused on characterizing the intrinsic cardiomyogenic activity in a variety of adult-derived stem cells. We have also invested considerable effort in developing strategies to promote cardioprotection. For example, we have identified genetic pathways which reduce cardiomyocyte apoptosis, particularly in response to cell cycle activation. In addition, we have studied the mechanism of anthracycline-induced cardiotoxicity, and have demonstrated that acute cardiotoxicity following doxorubicin (DOX) administrations results from p53-mediated inhibition of mTOR activity. Moreover, we have generated a juvenile mouse model exhibiting both acute and chronic DOX cardiotoxicity. Our current efforts are focused on identifying the mechanisms which contribute to "DOX memory" (that is, the mechanisms by which transient drug exposure gives rise to heart failure years after the cessation of treatment).

Funding

1. Principal Investigator: "Cell cycle activation for cardiac repair" (NIH R01 HL109205) [07/2011 - 06/2016] Studies proposed in this application will establish the mechanism by which D-type cyclins regulate cardiomyocyte cell cycle entry, and the degree to which targeted expression of cyclin D2 is able to promote myocardial regeneration. The overall goal is to gain an understanding of how cell cycle regulatory pathways can be manipulated to promote the repair of injured hearts.

2. Principal Investigator: "Genetic enhancement of cardiac repair with adult stem cells" (NIH R01 HL083126) [09/2011 - 08/2016] This grant is concerned with enhancing the capacity of Sca-1 expressing progenitor cells to survive and proliferated following cardiomyogenic differentiation in vivo.

The Field Lab
The Field lab