mark gillespie phd

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• Medical Sciences Building 5851 USA Drive North MSB 3344 Mobile, AL 36688

Mark N. Gillespie, Ph.D.

Dr. Mark N. Gillespie, Professor, received his Baccalaureate in Physiology and Ph.D. in Pharmacology from the University of Kentucky in Lexington, KY, and completed his postdoctoral fellowship in the Cardiovascular Pulmonary Research Lab at the University of Colorado in Denver, CO.  Dr. Gillespie chaired of the Department of Pharmacology at the Frederick P. Whiddon College of Medicine from 1995 to 2023.

Research in the Gillespie laboratory focuses on defining novel biological roles of oxidative injury or modification to the two cellular genomes, mitochondrial (mt) and nuclear DNA, in governing the life and death of lung cells.  One series of studies tests the idea that mtDNA functions as a "sentinel" molecule in which excessive damage caused by toxic oxygen radicals serves to activate cell death pathways.  In an extension of this idea, we also are exploring the prospect that mtDNA repair pathways could emerge as isolated targets for pharmacologic intervention in acute lung injury.  In contrast to oxidative damage to mtDNA, which occurs in the setting of toxicity, oxidants generated in the context of normal cell signaling do not alter mitochondrial DNA integrity, but surprisingly cause sequence-specific base modifications in nuclear genes.  Because these oxidative modifications are clustered in promoter regions of inducible genes, our second major project tests the idea that oxidative DNA modifications accompanying physiological signals modify the topography and protein binding of functionally important DNA sequences and thereby influence gene regulation. This general hypothesis is tested experimental systems ranging in complexity from cultured lung cells to human lung tissue specimens from patients with COPD, idiopathic pulmonary hypertension, and other pulmonary disorders. These studies are significant because they have identified a new level of oxidant regulation of cell function at the level of the genome, and perhaps more importantly, because they point to links between normal cell signaling and somatic mutation underlying both malignant and non-malignant lung diseases.

Publications

Daly GT, Pastukh VM, Tan YB, Francis CM, Aggen CZ, Groark SC, Edwards C, Mulekar MS, Hamo M, Simmons JD, Kutcher ME, Hartsell EM, Dinwiddie DL, Turpin ZM, Bass HW, Roberts JT, Gillespie MN, Langley RJ. Novel attributes of cell-free plasma mitochondrial DNA in traumatic injury. Clin Transl Med. 2022 Oct;12(10):e1055. doi: 10.1002/ctm2.1055. PubMed PMID: 36245326; PubMed Central PMCID: PMC9574491.

Hepokoski ML, Odish M, Lam MT, Coufal NG, Rolfsen ML, Shadel GS, Moyzis AG, Sainz AG, Takiar PG, Patel S, Leonard AJ, Samandari N, Hansen E, Trescott S, Nguyen C, Jepsen K, Cutter G, Gillespie MN, Spragg RG, Sasik R, Ix JH. Absolute quantification of plasma mitochondrial DNA by droplet digital PCR marks COVID-19 severity over time during intensive care unit admissions. Am J Physiol Lung Cell Mol Physiol. 2022 Jul 1;323(1):L84-L92. doi: 10.1152/ajplung.00128.2022. Epub 2022 Jun 14. PubMed PMID: 35699291; PubMed Central PMCID: PMC9273271.

Hartsell EM, Gillespie MN, Langley RJ. Does acute and persistent metabolic dysregulation in COVID-19 point to novel biomarkers and future therapeutic strategies?. Eur Respir J. 2022 Feb;59(2). doi: 10.1183/13993003.02417-2021. Print 2022 Feb. PubMed PMID: 34675049; PubMed Central PMCID: PMC8542864.

Longnus SL, Rutishauser N, Gillespie MN, Reichlin T, Carrel TP, Sanz MN. Mitochondrial Damage-associated Molecular Patterns as Potential Biomarkers in DCD Heart Transplantation: Lessons From Myocardial Infarction and Cardiac Arrest. Transplant Direct. 2022 Jan;8(1):e1265. doi: 10.1097/TXD.0000000000001265. eCollection 2022 Jan. PubMed PMID: 34934807; PubMed Central PMCID: PMC8683216.

Langley RJ, Migaud ME, Flores L, Thompson JW, Kean EA, Mostellar MM, Mowry M, Luckett P, Purcell LD, Lovato J, Gandotra S, Benton R, Files DC, Harrod KS, Gillespie MN, Morris PE. A metabolomic endotype of bioenergetic dysfunction predicts mortality in critically ill patients with acute respiratory failure. Sci Rep. 2021 May 18;11(1):10515. doi: 10.1038/s41598-021-89716-0. PubMed PMID: 34006901; PubMed Central PMCID: PMC8131588.

Migaud M, Gandotra S, Chand HS, Gillespie MN, Thannickal VJ, Langley RJ. Metabolomics to Predict Antiviral Drug Efficacy in COVID-19. Am J Respir Cell Mol Biol. 2020 Sep;63(3):396-398. doi: 10.1165/rcmb.2020-0206LE. PubMed PMID: 32574504; PubMed Central PMCID: PMC7462337.

Williams JD, Houserova D, Johnson BR, Dyniewski B, Berroyer A, French H, Barchie AA, Bilbrey DD, Demeis JD, Ghee KR, Hughes AG, Kreitz NW, McInnis CH, Pudner SC, Reeves MN, Stahly AN, Turcu A, Watters BC, Daly GT, Langley RJ, Gillespie MN, Prakash A, Larson ED, Kasukurthi MV, Huang J, Jinks-Robertson S, Borchert GM. Characterization of long G4-rich enhancer-associated genomic regions engaging in a novel loop:loop 'G4 Kissing' interaction. Nucleic Acids Res. 2020 Jun 19;48(11):5907-5925. doi: 10.1093/nar/gkaa357. PubMed PMID: 32383760; PubMed Central PMCID: PMC7293029.

Rieske RR, Kutcher ME, Audia JP, Carter KT, Lee YL, Tan YB, Gillespie MN, Capley GC, Tatum DM, Smith AA, Duchesne JC, Simmons JD. Analysis of Plasma Products for Cellular Contaminants: Comparing Standard Preparation Methods. J Am Coll Surg. 2020 Apr;230(4):596-602. doi: 10.1016/j.jamcollsurg.2019.12.042. PubMed PMID: 32220451; PubMed Central PMCID: PMC7682813.

Tan YB, Pastukh VM, Gorodnya OM, Mulekar MS, Simmons JD, Machuca TN, Beaver TM, Wilson GL, Gillespie MN. Enhanced Mitochondrial DNA Repair Resuscitates Transplantable Lungs Donated After Circulatory Death. J Surg Res. 2020 Jan;245:273-280. doi: 10.1016/j.jss.2019.07.057. Epub 2019 Aug 14. PubMed PMID: 31421373; PubMed Central PMCID: PMC6900440.

• Register for Orientation
• Interactive
• JagTran Tracker
• JagMail Login
• Faculty & Staff
• Directories
• Faculty/Staff

• College of Medicine
• Departments
• Pharmacology

• Email Address:
• [email protected]
• Phone Number:
• (251) 460-6784
• Medical Sciences Building 5851 USA Drive North MSB 3344 Mobile, AL 36688

Mark N. Gillespie, Ph.D.

Dr. Mark N. Gillespie, Professor, received his Baccalaureate in Physiology and Ph.D. in Pharmacology from the University of Kentucky in Lexington, KY, and completed his postdoctoral fellowship in the Cardiovascular Pulmonary Research Lab at the University of Colorado in Denver, CO.  Dr. Gillespie chaired of the Department of Pharmacology at the Frederick P. Whiddon College of Medicine from 1995 to 2023.

Research in the Gillespie laboratory focuses on defining novel biological roles of oxidative injury or modification to the two cellular genomes, mitochondrial (mt) and nuclear DNA, in governing the life and death of lung cells.  One series of studies tests the idea that mtDNA functions as a "sentinel" molecule in which excessive damage caused by toxic oxygen radicals serves to activate cell death pathways.  In an extension of this idea, we also are exploring the prospect that mtDNA repair pathways could emerge as isolated targets for pharmacologic intervention in acute lung injury.  In contrast to oxidative damage to mtDNA, which occurs in the setting of toxicity, oxidants generated in the context of normal cell signaling do not alter mitochondrial DNA integrity, but surprisingly cause sequence-specific base modifications in nuclear genes.  Because these oxidative modifications are clustered in promoter regions of inducible genes, our second major project tests the idea that oxidative DNA modifications accompanying physiological signals modify the topography and protein binding of functionally important DNA sequences and thereby influence gene regulation. This general hypothesis is tested experimental systems ranging in complexity from cultured lung cells to human lung tissue specimens from patients with COPD, idiopathic pulmonary hypertension, and other pulmonary disorders. These studies are significant because they have identified a new level of oxidant regulation of cell function at the level of the genome, and perhaps more importantly, because they point to links between normal cell signaling and somatic mutation underlying both malignant and non-malignant lung diseases.

Publications

Daly GT, Pastukh VM, Tan YB, Francis CM, Aggen CZ, Groark SC, Edwards C, Mulekar MS, Hamo M, Simmons JD, Kutcher ME, Hartsell EM, Dinwiddie DL, Turpin ZM, Bass HW, Roberts JT, Gillespie MN, Langley RJ. Novel attributes of cell-free plasma mitochondrial DNA in traumatic injury. Clin Transl Med. 2022 Oct;12(10):e1055. doi: 10.1002/ctm2.1055. PubMed PMID: 36245326; PubMed Central PMCID: PMC9574491.

Hepokoski ML, Odish M, Lam MT, Coufal NG, Rolfsen ML, Shadel GS, Moyzis AG, Sainz AG, Takiar PG, Patel S, Leonard AJ, Samandari N, Hansen E, Trescott S, Nguyen C, Jepsen K, Cutter G, Gillespie MN, Spragg RG, Sasik R, Ix JH. Absolute quantification of plasma mitochondrial DNA by droplet digital PCR marks COVID-19 severity over time during intensive care unit admissions. Am J Physiol Lung Cell Mol Physiol. 2022 Jul 1;323(1):L84-L92. doi: 10.1152/ajplung.00128.2022. Epub 2022 Jun 14. PubMed PMID: 35699291; PubMed Central PMCID: PMC9273271.

Hartsell EM, Gillespie MN, Langley RJ. Does acute and persistent metabolic dysregulation in COVID-19 point to novel biomarkers and future therapeutic strategies?. Eur Respir J. 2022 Feb;59(2). doi: 10.1183/13993003.02417-2021. Print 2022 Feb. PubMed PMID: 34675049; PubMed Central PMCID: PMC8542864.

Longnus SL, Rutishauser N, Gillespie MN, Reichlin T, Carrel TP, Sanz MN. Mitochondrial Damage-associated Molecular Patterns as Potential Biomarkers in DCD Heart Transplantation: Lessons From Myocardial Infarction and Cardiac Arrest. Transplant Direct. 2022 Jan;8(1):e1265. doi: 10.1097/TXD.0000000000001265. eCollection 2022 Jan. PubMed PMID: 34934807; PubMed Central PMCID: PMC8683216.

Langley RJ, Migaud ME, Flores L, Thompson JW, Kean EA, Mostellar MM, Mowry M, Luckett P, Purcell LD, Lovato J, Gandotra S, Benton R, Files DC, Harrod KS, Gillespie MN, Morris PE. A metabolomic endotype of bioenergetic dysfunction predicts mortality in critically ill patients with acute respiratory failure. Sci Rep. 2021 May 18;11(1):10515. doi: 10.1038/s41598-021-89716-0. PubMed PMID: 34006901; PubMed Central PMCID: PMC8131588.

Migaud M, Gandotra S, Chand HS, Gillespie MN, Thannickal VJ, Langley RJ. Metabolomics to Predict Antiviral Drug Efficacy in COVID-19. Am J Respir Cell Mol Biol. 2020 Sep;63(3):396-398. doi: 10.1165/rcmb.2020-0206LE. PubMed PMID: 32574504; PubMed Central PMCID: PMC7462337.

Williams JD, Houserova D, Johnson BR, Dyniewski B, Berroyer A, French H, Barchie AA, Bilbrey DD, Demeis JD, Ghee KR, Hughes AG, Kreitz NW, McInnis CH, Pudner SC, Reeves MN, Stahly AN, Turcu A, Watters BC, Daly GT, Langley RJ, Gillespie MN, Prakash A, Larson ED, Kasukurthi MV, Huang J, Jinks-Robertson S, Borchert GM. Characterization of long G4-rich enhancer-associated genomic regions engaging in a novel loop:loop 'G4 Kissing' interaction. Nucleic Acids Res. 2020 Jun 19;48(11):5907-5925. doi: 10.1093/nar/gkaa357. PubMed PMID: 32383760; PubMed Central PMCID: PMC7293029.

Rieske RR, Kutcher ME, Audia JP, Carter KT, Lee YL, Tan YB, Gillespie MN, Capley GC, Tatum DM, Smith AA, Duchesne JC, Simmons JD. Analysis of Plasma Products for Cellular Contaminants: Comparing Standard Preparation Methods. J Am Coll Surg. 2020 Apr;230(4):596-602. doi: 10.1016/j.jamcollsurg.2019.12.042. PubMed PMID: 32220451; PubMed Central PMCID: PMC7682813.

Tan YB, Pastukh VM, Gorodnya OM, Mulekar MS, Simmons JD, Machuca TN, Beaver TM, Wilson GL, Gillespie MN. Enhanced Mitochondrial DNA Repair Resuscitates Transplantable Lungs Donated After Circulatory Death. J Surg Res. 2020 Jan;245:273-280. doi: 10.1016/j.jss.2019.07.057. Epub 2019 Aug 14. PubMed PMID: 31421373; PubMed Central PMCID: PMC6900440.

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Mark Gillespie, PhD

Change in all things is sweet.” So said Aristotle, and Mark Gillespie, PhD, professor and chairman of Department of Pharmacology at University of South Alabama, could not agree more. In fact, Dr. Gillespie says it is the ability to change direction and explore new areas of interest in his own profession that make every day of work so enjoyable.

“One of the best parts of this job is that I am able to change what I do—to sort of reinvent myself and follow my ideas and dreams,” he said.

Dr. Gillespie was drawn to pharmacology soon after entering college, when he was considering a career as a physician. “Early in my college career, I met a couple of professors who were doing work in pharmacology that I thought was very interesting,” he recalled. “They gave me jobs in their labs and I found I really enjoyed the work.”

After receiving his bachelor’s degree at the University of Kentucky (UK), Dr. Gillespie received his PhD at the university’s College of Pharmacy before moving to the University of Colorado Health Sciences Center to complete his postdoctoral fellowship at the center’s cardiovascular-pulmonary research lab.

“Lou Diamond, one of the pioneers of pulmonary mechanics measurement in small lab animals, was one of my mentors, and working with him heralded the opportunity to look at drugs in animal models in a detailed way that, until then, hadn’t been easy to do,” Dr. Gillespie said.

After completing his postdoctoral work, Dr. Gillespie returned to his alma mater, UK College of Pharmacy’s Division of Pharmacology and Experimental Therapeutics, where he spent nearly 10 years before moving to the University of South Alabama.

“Coming to the University of South Alabama was an easy choice for me,” he said. “From a professional perspective, the university has always been on the cutting-edge of pulmonary research, and has put a long list of researchers on the map.”

The city of Mobile, which is located close to the Gulf of Mexico, and offers a great arts community and a diverse population, was also a draw. “For me, it was a ‘no-brainer’ to come down to a hotbed of pulmonary research and essentially live on the beaches,” he explained.

Dr. Gillespie said that while some aspects of his work have changed during his more than two decades as a pharmacologist and department chair, others are remarkably similar to when he began his career.

“First and foremost, I’m a scientist, and although the research topics and funding environment have changed, being a scientist and working with students and postdoctoral fellows is still a great pleasure,” he said.

In the years since he earned his PhD, translational science has emerged as the primary focus of researchers around the world, he added. “In fact, the recent international emphasis on translational research is one of the reasons the ATS is becoming increasingly important to scientists like me,” Dr. Gillespie noted. “By bringing bench scientists in closer contact with physicians at the bedside, the ATS has really aided the field and moved it forward, ensuring that research remains timely and competitive.”

While noting that he has been fortunate to work in many different areas of biology during his career, Dr. Gillespie is most proud of the work he has conducted on signal transduction, which he started early in his career.

Back in the 1980s, he collaborated with Jack Olson, from the University of South Alabama College of Medicine in examining signaling pathways in pulmonary hypertension. “At that time, the concept of studying signal transduction as a pharmacological target in pulmonary hypertension was fairly new,” he recalled. According to Dr. Gillespie, they were among the first individuals to begin to look at signaling pathways as a target for intervention.”

Today, his research focuses on defining novel biological roles of oxidative injury or modification to the two cellular genomes, mitochondrial (mt) and nuclear DNA, in governing the life and death of lung cells. “We’ve found that normal signaling carries with it a targeted oxidative threat to our genomes. This finding has tremendous implications and I’m excited about the possibility that DNA repair pathways are legitimate pharmacological targets in lung diseases,” Dr. Gillespie explained.

Research in the Gillespie lab has been supported by the NIH for nearly his entire career. Most recently, the group has attracted a small business development grant, as well as other funding, to promote development of novel drugs that target mitochondrial DNA repair pathways. “Being a medical scientist has allowed me the opportunity to reinvent myself and do new things, which in turn enables me to remain excited about what I do,” he concluded. “This research in DNA damage in signaling and in disease is, I think, an interesting story.”