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Brian Nelson Griffith, Ph.D.

Brian Nelson Griffith, Ph.D.
Associate Professor of Biomedical Science
Teaching: Biochemistry and Nutrition
Mentor: Lisa M. Salati, Ph.D.

Email: bgriffith@osteo.wvsom.edu
Office: A-314
Phone: (304) 647-6225
Fax: (304) 645-4859
Cell Phone: 304-661-4993


Education / Training

Ph.D from West Virginia University School of Medicine

M.S. from West Virginia University; Morgantown, WV

B.S. in biology and B.A. in chemistry from Alderson-Broaddus College; Philippi, WV

Research Interests - Project #1: Cardiovascular Research

The overall goal of our current research project is to identify new pharmacological and nutrition therapies for the prevention of myocardial infarction induced cell death.

An osteopathic physician's first and last duty in patient care according to Dr. Andrew Taylor Still is to "look well to a healthy blood-and-nerve supply." The ability of the heart to maintain healthy blood and aerobic metabolism is important for maintaining cellular homeostasis as well as cardiac structure and function. Therefore, when a person experiences a myocardial infarction (MI), reestablishing blood flow to the ischemic area is essential in order to preserve cardiac structure and function.

Reperfusion therapy, caused by restoring blood flow to the ischemic area, can ironically cause myocardial cell death by activating cell apoptosis and/or cell necrosis. Thus, reperfusion therapy can cause structural damage to the heart, alternations in cardiac function, the development of heart failure and ultimately death. Therefore our laboratory is interested in investigating new pharmacological and nutritional therapies to prevent post-MI-induced-IR injury caused by reperfusion therapy. Thus, our ultimate goal is to restore cellular homeostasis following IR-injury.


  1. Ischemia-Reperfusion Injury: Myocardial ischemic injury results from severe impairment of coronary blood supply and produces a variety of clinical syndromes.
  2. Apoptosis is defined as programmed cell death, and is regulated by a very complex pathway of pro-apoptotic and anti-apoptotic proteins.
  3. Necrosis occurs when a cell is damaged by an external force, such as ischemia-reperfusion injury. When cells die from necrosis, it's a rather messy affair. The death causes inflammation that can cause further distress or injury within the body.

Funding source:

The study described above is funded by a WVSOM intramural grant.

General Description of our Current Research Projects:

One consequence of IR injury in the heart is oxidative stress with the subsequent depletion of NAD+ levels. We have previously shown that niacin (Vitamin B3), a precursor for NAD+, reduces IR-induced apoptosis. The question of how NAD+ depletion contributes to IR-injury is unknown but may involve SIRT1, a type III, NAD-dependent histone deacetylase (HDAC) and one of its downstream targets, the transcription factor NFκB. Therefore, we plan to explore the role of SIRT1 and NFκB in IR injury.

Resveratrol, a compound found in red wine, is known to have anti-aging, anti-oxidant, and more importantly, cardioprotective effects. It has been shown to work via several downstream targets including SIRT1. However, the involvement of SIRT1 in the cardioprotective effect of resveratrol is still not understood. Therefore, we explored the effect of both resveratrol and the selective SIRT1 activators, DCHC and Cay10591, on IR injury in HL-1 cells. Our initial studies demonstrate that both DCHC and Cay10591 reduce IR-induced caspase-3 activity, a biomarker of cellular apoptosis.

Other targets being explored in our laboratory include NFκB, a master controller of inflammatory cytokine and chemokine production. Recently, it was shown that SIRT1 activity in adipose tissue controls NFκB activity, as demonstrated by siRNA knockout animals and transgenic knockout animals. Therefore, since inflammation plays a major role in IR injury and progression to heart failure, we propose to explore the connection between SIRT1 activity, NFκB transcriptional activity, and IR injury in cardiac myocytes.


Our laboratory uses a variety of molecular, histological, and biochemical approaches to study IR injury. To begin with we use an in vitro cell line referred to as HL-1 cardiac myocytes to study the effects of different agents on IR-injury. We also use flow cytometry which quantifies apoptotic and necrotic cell populations (see figure 2). And, lastly we use an in vivo mouse model of IR-injury. Basically, we occlude the left descending coronary artery (LAD) of a mouse heart and then measure the infarct size and collagen deposition through a series of histological stains. In addition, we also use echocardiography to measure cardiac parameters. It is our goal to find a pharmacological or nutrition agent which reduces IR-injury in both an in vivo and in vitro model.

Project 1c:

An interesting project in our laboratory involves aging. Most myocardial infarctions typically occur in older human patients; however most of the research involving mouse models use young animals. Thus we are interested in exploring the effects of aging on cardiac parameters in an attempt to study the effects of IR-injury in young versus old animals. It is our hypothesis that older animals will show a more profound effect of IR-injury as opposed to younger animals.

Participating Faculty, Staff and Students:

Our research team includes Dr. Judith Maloney, a collaborator from Marquette University, Bethany Hampton, Millie Mattox and multiple WVSOM students.

Research Interests - Project #2: Public Health Related Project

As a public health research project, we are interested in evaluating the disparity between self-perceived health and health status and behaviors in rural Appalachia.

The area of rural Appalachia was demarcated in 1965 by the Appalachian Regional Commission. This area consists of 365 counties in 12 states and all 55 counties of West Virginia. The Appalachia region is one of the unhealthiest regions in the United States. Our research was the first to show a disparity between self-perceived health and health status and behaviors within rural Appalachia.

It is our goal to improve the health status of rural Appalachians, by stimulating a change in the public health message and health programs targeted at rural Appalachians.


Dr. Wayne Miller.

Research Support:

This research is supported by the West Virginia School of Osteopathic Medicine.

Research Publications

  1. Griffith B, Canfield P. Biochemistry and Pathology of Bleeding: An Integrative Approach to Team-Based Learning. MedEdPORTAL Publications; 2015. Available from: https://www.mededportal.org/publication/10099#sthash.OBvA6AHc.KJyIrXHv.dpuf
  2. Griffith, B. (2014, November 24). Application Exercise on Oxidative Phosphorylation and Ischemia-Reperfusion Injury. Retrieved May 5, 2015, from Life Science Teaching Resource Community Web site: http://www.lifescitrc.org/resource.cfm?submissionID=9807
  3. Griffith, B., Miller, W. (2014, November 24). Jeopardy Application Exercise on Basic Nutrition, Exercise, Obesity, and Lifestyle Changes. Retrieved May 5, 2015, from Life Science Teaching Resource Community Web site: http://www.lifescitrc.org/resource.cfm?submissionID=9805
  4. Miller, WC. Griffith, BN, Bikman, TJ, Meyer, CM. Misconceptions about health and disease prevent behavior of rural Appalachian Americans. International Journal of Medicine. 2014 2(2): 71-75.
  5. Griffith BN, Montalto NJ, Ridpath L, Sullivan K. Tobacco dependence curricula in US osteopathic medical schools: a follow-up study. J Am Osteopath Assoc. 2013 Nov;113(11):838-48.
  6. Cyphert TJ, Suchanek AL, Griffith BN, Salati LM. Starvation actively inhibits splicing of glucose-6-phosphate dehydrogenase mRNA via a bifunctional ESE/ESS element bound by hnRNP K. Biochim Biophys Acta. 2013 Sep;1829(9):905-15.
  7. Griffith BN, Lovett GD, Pyle DN 2nd, Miller WC. Self-rate health in rural Appalachia: health perceptions are incongruent with health status and health behaviors. BMC Public Health 2011 April 13:11 (1) 229.
  8. Zhang M, Liu H, Tian Z, Griffith BN, Ji M, Li QQ. Gossypol induces apoptosis in human PC-3 prostate cancer cells by modulating caspase-dependent and caspase-independent cell death pathways. Life Science. January 2007. 80(8) pages 767-74.
  9. Zhang M, Ling Y, Yang CY, Liu H, Want R, Wu X, Ding K, Zhu F, Griffith BN, Mohammad RM, Wang S, Yang D. A novel Bcl-2 small molecule inhibitor 4-(3-methoxy-phenylsulfannyl-7-nitro-benzofurazan-3-oxide (MNB)-induced apoptosis in leukemia cells. Annuals of Hematology July 2007, 86(7): 471-81.
  10. Zhang M, Fang X, Liu H, Guo R, Wu X, Li B, Zhu F, Ling Y, Griffith BN, Wang S, Yang D. Bioinformatics-based discovery and characterization of AKT-selective inhibitor 9-chloro-2-methylellipticinium acetate (CMEP) in breast cancer cells. Cancer Letters. July 2007. 19:252(2):244-58.
  11. Griffith BN, Walsh CM, Szeszel-Fedorowicz W, Timperman, A and Salati LM. Identification of hnRNPs K, L and A2/B1 as candidate proteins involved in the nutritional regulation of mRNA splicing. Biochim Biophys Acta. 2006 Nov-Dec;1759(11-12):552-61.
  12. Szeszel-Fedorowicz W, Talukdar I, Griffith BN, Walsh CM, Salati LM. An exonic splicing silencer is involved in the regulated splicing of glucose-6-phosphate dehydrogenase mRNA. J Biol Chem. 2006 Nov 10;281(45):34146-58.
  13. Martirosyan A, Leonard S, Shi X, Griffith BN, Gannett P, Strobl J. Actions of a Histone Deacetylase Inhibitor, NSC3852, Reactive Oxygen Species to Cell Differentiation and Apoptosis in MCF-7 Human Mammary Tumor Cells. J Pharmacol Exp Ther. 2006 Feb 23
  14. Waggoner JR, Huffman J, Griffith BN, Jones LR, Mahaney JE. Improved expression and characterization of Ca2+-ATPase and phospholamban in High-Five cells. Protein Experimental Purification. 2004 Mar;34(1):56-67.