Laboratory of Cardiac Disease, Redox Signaling and Cell Regeneration (Ivor J. Benjamin, Director)

Our laboratory focuses on the pathogenic mechanisms involving selected stress response pathways (e. g., heat shock response, redox state) induced at onset of disease and their subsequent dysregulation culminating in disease progression. We are specifically interested in deciphering the genetic, molecular and metabolic events that promote adverse remodeling in response to acquired conditions (e.g., heart attacks) and inheritable (e.g., cardiomyopathy) disorders. From such insights of the causal mechanisms using complementary model systems (i.e., yeast, flies, mice), our multidisciplinary program and translational studies are seeking to exploit innovative strategies (e.g., small molecule targeting, cell regeneration) for diagnostic, therapeutic, and ultimately disease prevention.


group

IJBWork in our laboratory focuses on three complementary themes linked to protein misfolding diseases: 1) small heat shock proteins (sHSPs) and heart failure, 2) redox biology and gain of ‘toxic’ function mechanisms in aggregation-prone diseases, and 3) stem and human iPSCs for cellular regeneration.

hsf

1) Alzheimer’s disease is a well-known protein misfolding disorder but few research scientists recognize that heart failure shares similar pathogenic mechanism(s). Our longstanding interests in the roles of small HSPs, which double as molecular chaperones, are focusing on what mechanisms govern the fate by which acquired (e.g., heart attacks) and/or inherited (e.g., hypertrophic cardiomyopathy) conditions lead to heart failure. Using transgenic and knockout mouse technology, this line of investigation might explain how chaperone-like functions of HSPs might ultimately be exploited therapeutically to speed the physiological recovery in tissues damaged after a heart attack.

2) Many results of numerous antioxidants in clinical trials have failed to show therapeutic benefits. We have recently discovered a new disease mechanism: “reductive stress” that challenges the existing paradigm of oxidative stress.  In transgenic mice recapitulating a protein-misfolding cardiomyopathy associated with myofibrillar disease in humans, we have demonstrated that decreasing the function of glucose-6-phosphate dehydrogenase (G6PD), an antioxidant that generatemitos the reductant NADPH, “cures” the disease in mice by ameliorating reductive stress, aggressome formation, hypertrophy, heart failure and death. Ours collaborative studies in complementary model systems (e.g., flies, yeast, mice) are seeking to identify other disease-causing mutations and their potential interacting pathways that either increase resistance and/or decrease susceptibility in disease pathogenesis.

3) Development of human induced pluripotent stem cells (iPSCs) derived from adult somatic cells entirely circumvents usage of embryonic stem cells. We are testing the hypothesis that the pathogenic transition of cardiac and neurodegenerative diseases are Hips Cell Clone Imagecausally related to dysregulation of stress response and anti-oxidative pathways, linked to macromolecular damage, in adult stem and progenitor cells. After recent sabbatical training at the Mass General Hospital/Harvard Stem Cell Institute and Gladstone Institute forCardiovascular Research/UCSF, Dr. Benjamin and colleagues are pursuing investigations 1) to understand redox-signaling mechanisms influencing cardiac  differentiation in human iPSC and 2) to model disease-specific iPSCs from patients with myofibrillar disease. To achieve the latter aim, we are seeking collaborators to establish an international consortium for modeling rare myofibrillar and related diseases using our iPSC platform technology.

Graduate students and postdoctoral trainees can select from but are not limited to these ongoing projects in the Benjamin laboratory.  Please Visit our Contact Us page for employment opportunities.

Cardiologist Ivor J. Benjamin, MD, receives the prestigious NIH 2009 Pioneer Award.  This $2.5 million award will allow Dr. Benjamin and his laboratory team and colleagues to research how "reductive stress" may damage the heart and other organs.  Read the September 24, 2009 News Article

   Laboratory Director

 

Dr. Ivor Benjamin

Ivor J. Benjamin, MD, FAHA, FACC
Professor of Medicine and Biochemistry
Christi T. Smith Endowed Chair for Cardiovascular Research
ivor.benjamin@hsc.utah.edu

   Current Lab Members:


Alison Ausman

Alison Ausman
Administrative Assistant
alison.ausman@hsc.utah.edu

Elisabeth Christians, DVM PhD

Elisabeth Christians, DVM, PhD
Research Associate Professor
elisabeth.christians@hsc.utah.edu

David Coe

David Coe
Lab Technician
david.coe@hsc.utah.edu

 

Katie Mitelfelt, PhD Student

Katie Mitzelfelt, PhD Student
Graduate Student
katie.A.Barber@utah.edu

Soumyajit Banerjee Mustafi, PhD

Soumyajit Banerjee Mustafi, PhD

Post Doctoral Research Associate
soumyajit.mustafi@hsc.utah.edu

Greg Pratt

Greg Pratt 
Sr Laboratory Specialist
greg.pratt@hsc.utah.edu

Michael Riedel, PhD

Michael Riedel, PhD
Post Doctoral Research Associate
michael.riedel@utah.edu


Graydon Taylor, Undergraduate Student

Graydon Taylor, Undergrad
Research Assistant
graydon.taylor@hsc.utah.edu

Xiaohui Wang, MD, PhD

Xiaohui Wang, MD, PhD
Research Associate
xiaohui.wang@hsc.utah.edu

 

 

 

 

 

 

 

 


Lab Alumni:

John Erikson, MD, PhD - Fellow from 1992-1994
Current activities: Program Director, Cardiovascular Disease Fellowship, UTHSC San Antonio, Texas

Lie Shao, MD - Lab member from 1993-1995
Current activities: Pathology Residency, John Hopkins Hospital, Maryland

Jacqueline Brown, PhD - Fellow from 1994-1996
Current activities: Teacher, San Angelo, Texas

D. Randy McMillan - Lab member from 1994-1998
Current activities: Assistant Professor, Department of Pediatrics, White Lab, UTSW

Xiao-Xia Zuo, MD - Lab member from 1996-1999
Current activities: Staff physician, Hunan Hospital, China

Xianzhong Xiao - Fellow from 1996-1999
Current activities: Professor of Pathophysiology, Dean of Xiangya School of Medicine, Central South University, Changsha, Hunan, China

Bishop Curry - Fellow from 1996-1998
Current activities: Site Head, Executive Director of Comparative Medicine at Pfizer Pharmaceuticals. Site Head, Worldwide Comparative Medicine at Pfizer Pharmaceuticals. NCI-Animal Program Director / Animal Facility Operations and Veterinary Care at Science Applications International Corporation, Virginia

Alberta Davis - Fellow from 1997-1999
Current activities: Science writer, Alcon Pharmaceuticals

Li Liu - Medical student from 2000-2002
Current activities: Staff physician, Jiangso Medical University, Zhenjiang, China

Patrice Connell - Fellow from 2000-2003
Current activities:

Liang-Jun Yan - Fellow from 2000-2003
Current activities: Associate professor, University of Northern Texas Health Sciences Center

Sathya Srinivasan - Fellow from 2003-2005
Current activities: Staff scientist, University of Calgary, Alberta, Canada

Raj Sooroppan - Fellow from 2003-2006
Current activities: Research Assistant Professor, University of Utah School of Medicine

Ryan Taylor - Fellow from 2004-2007
Current activities: Medical Science Liasion, Actelion Pharmaceuticals US

Lensey Scott - Fellow from 2009-2011
Current activities: Research scientist, Mississippi State University

Takahiro Ishiwata, MD, PhD Fellow  from 2010 – 2011
Current activities:
 
Joel Pieper – Research Assistant from 2010-2012
Current activities:
 
Takashi Kanai – Fellow from 2011-2012
Current activities: 

Huali Zhang – Fellow from 2011-2012 
Current activities: 

Qiang Lui – Research Assistant from 2010-2012 
Current activities: 

Pattraranee Limphong – Fellow from 2009-2012 
Current activities: 


 

Selected Publications:

  • Limphong P, Zhang H, Liu Q, Christians E, Riedel M, Ivey K, Cheng P, Taylor G, Winge D, Srivastava D, Benjamin IJ. Modeling Protein Aggregation Cardiomyopathy using Murine Induced Pluripotent Stem Cells. Stem Cells Translational Medicine. (In revision)
  • Brewer AC, Mustafi SB, Murray T, Benjamin IJ. Reductive Stress Linked to Small HSPs, G6PD and NRF2 Pathways in Heart Disease. [Review]. Antioxidants & Redox Signaling. (Submitted)
  • Zhang H, Liu Q, Limphong P, Wende A, Wang X, Zhang X, Pratt GW, Schubert HL, Hill CP, Christians E, Benjamin IJ. Cataract-related Human CryAB Mutation Associated with Protein Aggregation Spares the Development of Desmin-related Cardiomyopathy in Mice. J Mol Cell Cardiol. (In Review)
  • Heng B. Xie HB, Cammarato A, Suggs JA, Lin H-C, Bernstein SI, Benjamin IJ#, Golic KG#. NADPH Metabolic Network regulates human aB-crystallin cardiomyopathy and reductive stress in Drosophila melanogaster. #Corresponding authors. PLoS Genet. (In Review)
  • Kim G, Meriin A, Gabai V, Christians E, Benjamin IJ, Wilson A, Wolozin B, Sherman M. The heat shock transcription factor Hsf1 is downregulated in DNA damage-associated senescence, contributing to the maintenance of senescence phenotype. Aging Cell. (In Press)

Association of Black Cardiologists award Dr. Ivor Benjamin the 2011 Dr. Daniel Savage Memorial Science Award


Dr.abc Benjamin was honored to receive the "2011 Dr. Daniel Savage Memorial Science Award" on October 29 from the Association of Black Cardiologists. Dr. Benjamin accepted the award at ABC's "Saving Hearts for Generations Dinner" in Washington, D.C. The award is ABC's highest honor, initiated in 1990 to recognize scientific achievement in the areas of cardiovascular disease and research. This annual award is named after Daniel D. Savage, M.D., PhD, who was heralded by his peers as the first to determine the role Left Ventricular Hypertrophy plays in cardiovascular disease.

Dr. Benjamin was awarded with the recognition of pioneering work in the areas of novel genetic pathways for cardioprotection; molecular and genetic analysis of heat shock transcription factors and their role in genetic development; and molecular mechanism of alpha B crystalline R1 20G familial cardiomyopathy.

Upcoming Events:

  • Dr. Ivor J. Benjamin will be presenting as invited speaker at the University of Kentucky Deans Distinguished Speaker Series on October 5, 2012. Lexington, Kentucky, USA.
  • Dr. Ivor J. Benjamin will be presenting as invited speaker at the University of South Alabama Distinguished Scientist Seminar on October 18, 2012. Mobile, Alabama, USA.
  • Dr. Ivor J. Benjamin will be presenting as invited speaker at the The 2012 Cardioprotection Colloquium.  November 2, 2102.  Los Angeles, California, USA.
  • Dr. Ivor J. Benjamin will be participating in the National Heart, Lung, and Blood Institute (NHLBI) Protein Workshop on November 19 & 20, 2012. Bethsesda, Maryland, USA.

Prior Events:

  • Dr. Ivor J. Benjamin presented a talk about "Heart  Throbs and Beats in the New Era of Stem Cells" on , at the University of Utah for the Women Investing in Service and Health Organization (WISH)March 29, 2009, Salt Lake City, Utah, USA
  • Read Dr. Ivor J. Benjamin's interview on how "Too much oxidant may lead to heart disease" by Lois M. Collins, Deseret News , Published Thursday, August 9, 2007, Salt Lake City, Utah, USA.
  • Dr. Andras Orosz presented at the 2nd World Conferfence of Stress. "Dual Roles of Heat Shock Factor 1 (HSF1) in Cardioprotection, Pathologic Hypertrophy and Heart Failure in Transgenic Mice."  August 23-26, 2007, Budapest, Hungary.

Mailing Address:

Dr. Ivor J. Benjamin
University of Utah
Division of Cardiology
Room 4A100
30 North 1900 East
Salt Lake City, UT 84132

(801) 581-7715

Request Materials:

NOTICE: Shipment of materials will be billed to recipient

Please provide Emory account number for mice or Fed Ex for cells

Dr. Benjamin's Lab Manager is:

Dr. Benjamin's administrative assistant is:

Please provide the following information, which will be used to initiate an MTA

  • Name of firm or institution requesting materials
  • Recipient contact person name, address, phone, e-mail

Please provide the following information for mice:

  • Institution requesting animals
  • Department address, phone, e-mail
  • Lab contact
  • Animal resource contact person
  • ARC phone, address for shipping, e-mail
  • Veterinarian name
  • Veterinarian phone, fax, e-mail

Health report will be faxed to the veterinarian of the receiving institution and any additional requirements will be discussed between institutions.

Fall 2012  All meetings to be held in the Renzetti Conference Room (Wintrobe Building, 7th floor South Corridor)

                                            September 2012

Wednesday September 19 - 9:00 AM:  Shayne Squires Presenting

Wednesday September 26 - 1:00 PM:  Soumyajit Mustafi Presenting - R120G (meeting via Google Web conference available)

October 2012

Wednesday October 10 - 9:00 AM:  Heng Xie Presenting - R120G

For general laboratory information:

Greg Pratt
Sr Laboratory Specialist & Lab Manager
Greg.Pratt@hsc.utah.edu
Phone:  801-581-6785
Fax:  801-585-1082

For general administrative inquiries:

Alison Ausman
Administrative Assistant to Dr. Ivor Benjamin
alison.ausman@hsc.utah.edu
Phone: 801-587-9785
Fax: 801-585-1082

EMPLOYMENT:

The Benjamin Lab currently has no open positions.


Our laboratory welcomes trainees at all levels (graduate students, medical students and postdoctoral clinical or basic research fellows) to join our multidisciplinary investigative team.

 Graduate and Postdoctoral Trainees: Please visit the University of Utah Bioscience program for more information on the Molecular Biology and Biological Chemistry Programs