PUCHOWICZ, MICHELLE A.

Associate Professor
Pediatrics-Obesity

Office: 318H TRANSLATIONAL RESEARCH BUILDING
71 SOUTH MANASSAS
MEMPHIS TN 38163
Tel: (901) 448-2007
mpuchowi@uthsc.edu

Education

  • PostDoc, CASE School of Medicine, Cleveland, Ohio, Anatomy & Nutritional Biochemistry
  • Ph.D., CASE School of Medicine, Cleveland, Ohio, Nutritional Biochemistry
  • M.S., CASE School of Medicine, Cleveland, Ohio, Nutritional Biochemistry
  • B.S., CASE School of Engineering, Cleveland, Ohio, Biomedical Engineering

Research Interest/Specialty

My research takes a targeted metabolic approach to studying regulatory pathways related to intermediary metabolism of brain and whole body energy metabolism. My background is multidisciplinary and diverse and includes expertise in nutrition and metabolism, biochemistry, and physiology of organ systems. My research focuses on the metabolic pathologies associated with the dysregulation of glucose and lipid metabolism, such as with obesity, insulin resistance and reperfusion/oxidative injury of organ systems. The use of stable isotope tracer and mass spectrometry technologies enables pathway discovery and discern metabolic and regulatory mechanisms that relate metabolic defects in fatty acid, protein, ketone body and/or glucose regulation; examples include those associated with oxidative injury, neuropathologies, and mitochondrial dysfunction.

My expertise on in-vivo studies and the use of stable-isotopes (2H2O, 18O, 17O) to study energy expenditure, lipid and protein turnover, as well as, the use of 13C and 2H labeled compounds for tracing of metabolic pathways of whole body and organ systems (such as adipose tissue), brings further knowledge to the study of energy metabolism. 

Research Description

My collaborative research efforts include studies of brain metabolism in rodent models of hypoxia, ischemia reperfusion injury and genetic mutations. The translational aspects of my work are aimed at obtaining a greater understanding of metabolic disturbances associated with oxidative stress and defects in energy metabolism of various organ systems, such as brain, liver and muscle.

I have continued service as an Instructor for the NIDDK sponsored annual international course on “Tracers in Metabolic Research: Principles and Practice of Kinetic Analysis”.  The use of stable isotope tracer and mass spectrometry technologies enables the discovery of regulatory mechanisms that relate tissue injury and mitochondrial dysfunction to defects in energy metabolism.

Studies include the use of rodent models of ketosis to investigate the role of ketone bodies as an alternate energy substrates, as well as their neuroprotective protective properties and mechanisms related to metabolic modulations associated with cell survival and function. 

Current Projects include: 

     Cell specific role of HIF1a on neuroprotection in mice

     Influence of Dietary Carbohydrate Restriction on Gut-Microbiota

     Effects of Diet induced ketosis on gut microbiome and stroke outcome

     Role of tissue-specific Cftr on glucose homeostasis

MPMS Facilities

As the Director of the Metabolic Phenotyping and Mass Spectrometry Facilities (MPMS), Division of Pediatric Obesity Program at UTHSC - Memphis, My philosophy as a scientist is to be resourceful and to assist fellow researchers in devising study plans to technically annotate the interrelated effects of metabolism on diabetes, obesity, inborn errors of metabolism and other metabolic related disorders, such as cancers.

MPMS Facility resides within the PMC Core, and specializes on the use of analytical platforms, such as GC and LC mass spectrometry, to study metabolic derangements of protein, carbohydrate, lipid and cholesterol metabolism. Our Analytical Team together with my expertise on the use of mass spectrometry and stable isotopomer analysis will bring additional novel analytical strategies that will help to delineate the metabolic complexities of many disorders investigated by our local research community. 

MPMS ANALYTICAL TEAM

Our collaborative team at UTHSC, Memphis, is a multi-disciplined resource group with converging focus on obesity and related pathologies and diseases:

 

Prahlad Rao, Ph.D.

Dr. Prahlad Rao is a Research Associate in Dr. Puchowicz’s lab and functions as a senior staff scientist in the MPMS. Dr. Rao has vast experience in understanding the functional aspects of complex metabolic diseases, such as obesity, through proteomics and metabolomics. He completed his doctoral studies at University of Illinois, Chicago where he gained his technical skills in mass spectrometry involving proteomics and metabolomics and pursued post-doctoral training at Texas Biomedical Research Institute, Dallas where he used targeted proteomic methods to identify and quantify specific transcription factors such as NFĸb. His is currently interested in understanding the role of gut bacteria in obesity and related diseases, and the changes associated with gut microbiota as a function of obesity. His multifaceted role in the laboratory includes developing mass spectrometry based metabolomic applications towards the MPMS facility and his own research projects aimed towards uncovering the crosstalk between gut microbiome and metabolic disorders. Click here to view his publications.

 

Aarti Sethuraman, Ph.D.

Dr. Aarti Sethuraman works as a Sr. Research Assistant Dr. Puchowicz’s lab since May 2018. She gained her Ph.D. working on uncovering hypoxia related metastatic pathways in breast cancer at Department of Pathology, University of Tennessee Health Science Center, Memphis. She has vast experience in mice colony maintenance and breeding, performing xenograft surgeries in rodent models and molecular biology techniques. Her research in our lab will focus on neuroprotective role of hypoxia in ketotic mice models. She also administrates sample acquisition and processing for the MPMS core. Click here to view her publications.

 

Atul Pranay, Ph.D.

Dr. Atul Pranay is currently a postdoctoral fellow in Dr. Puchowicz’s lab in the Department of Pediatrics, at the University of Tennessee Health Science Center, Memphis. He earned his Ph.D. in Department in Life Sciences at The Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) at Homi Bhabha National Institute. During his PhD, He worked to identify tumor markers for oral cancer and studied their utility in the prognosis of oral cancer. After his Ph.D., He worked in an industry where he developed LC-MS and ELISA assays for quantitation and characterization of Biosimilar molecules in biological samples. He was also involved in bioequivalence studies of drugs (therapeutic peptides and proteins) for their regulatory submission. He has extensive experience of Mass spectrometry, proteomics and molecular cloning. His research focuses on developing assays for study of bioactive metabolites by incorporation of stable isotope tracers to identify dysregulation in metabolic pathways. Click here to view his publications.

BOOK CHAPTERS

 1. Xu K, LaManna JC, and Puchowicz MA. Ketogenic Diet, Aging, and Neurodegeneration. In “Ketogenic Diet and Metabolic Therapies”, Expanded Roles in Health and Disease (ed. Masino SA), Oxford University Press, 216-226 (2017) 

2. LaManna JC, Puchowicz MA, Xu K, Harrison DK, and Bruley DF; Editors. Oxygen Transport to Tissue XXXII. In: Advances in Experimental Medicine and Biology (vol 701). Springer (2011) 

3. Kombu RS, Brunengraber H, and Puchowicz MA. Analysis of the Citric Acid Cycle Intermediates using Gas Chromatography-Mass Spectrometry In: Methods Molec Biol, “Metabolic Profiling: Methods and Protocols” (ed. Metz TO), Humana Press, 708:147-57. (2011)

4. Puchowicz MA, Koppaka SS, and LaManna JC. Brain Metabolic Adaptations to Hypoxia. In: Metabolic Encephalopathy (ed. McCandless DW), Springer 15-30 (2009) 

5. Zechel J, Lust W D, and Puchowicz M. Biochemical methods to assess the coupling of brain energy metabolism in control and diseased states. In: Methods Molec Biol v. 399, “Neuroprotection and Protocols”, (ed. Borsello T), Humana Press, 79-98 (2007)

CONTRIBUTIONS TO SCIENCE

 1.    Use of stable isotopes to study intermediary metabolism and novel pathways. Through my own research and collaborative efforts I have made major contributions to studying oxidative and biosynthesis metabolism, under normal and pathological conditions through the use stable isotope tracers and mass spectrometry techniques. Tracing substrate oxidation using 13C or 2H labeled substrates / compounds has enabled the understanding of anabolic and catabolic metabolism under altered metabolic conditions. This research has led to novel discovery of catabolic pathways in liver and brain.

a.    Cordoba-Chacon J, Majumdar N, List EO, Diaz-Ruiz A, Frank SJ, Manzano A, Bartrons R, Puchowicz M, Kopchick JJ, Kineman RD.Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice. Diabetes. (2015) Sep;64(9):3093-103. PMCID: PMC4542445

b.    Jin Z, Berthiaume JM, Li Q, Henry F, Huang Z, Sadhukhan S, Gao P, Tochtrop GP, Puchowicz MA, Zhang GF. Catabolism of (2E)-4-Hydroxy-2-nonenal via ω- and ω-1-Oxidation Stimulated by Ketogenic Diet. J Biol Chem. (2014) 289(46):32327-38. PMCID:PMC4231705

c.    Harris SR, Zhang GF, Sadhukhan S, Wang H, Shi C, Puchowicz MA, Anderson VE, Salomon RG, Tochtrop GP, Brunengraber H. Metabolomics and Mass Isotopomer Analysis as a Strategy for Pathway Discovery: Pyrrolyl and Cyclopentenyl Derivatives of the Pro-Drug of Abuse, Levulinate. Chem Res Toxicol. (2012) 26(2): 213-20. PMCID:PMC3997259

d.    Li Q, Tomcik K, Zhang S, Puchowicz MA, Zhang GF. Dietary regulation of catabolic disposal of 4-hydroxynonenal analogs in rat liver. Free Radic Biol Med. (2012); 52(6): 1043-53. PMCID:PMC3289253

 

2. Study of metabolism in vivo / in vitro: Use of stable isotopes to study intermediary metabolism. Another focus area of my research emphasizes metabolic pathology of glucose, lipid and protein metabolism such as with obesity, insulin resistance and metabolic syndrome. Through collaborative efforts, I have made major contributions to studying oxidative and biosynthesis metabolism, under normal and pathological conditions through the use stable isotope tracers and mass spectrometry techniques. Stable isotope technology and application enabled the measurements biosynthesis of cellular protein and lipids under altered metabolic conditions.

a.    Mera P, Laue K, Ferron M, Confavreux C, Wei J, Galán-Díez M, Lacampagne A, Mitchell SJ, Mattison JA, Chen Y, Bacchetta J, Szulc P, Kitsis RN, de Cabo R, Friedman RA, Torsitano C, McGraw TE, Puchowicz M, Kurland I, Karsenty G. Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise. Cell Metab. Jun 14;23(6):1078-92. (2016) PMCID:PMC4910629

b.    Krokowski D, Han J, Saikia M, Majumder M, Yuan CL, Guan BJ, Bevilacqua E, Bussolati O, Bröer S, Arvan P, Tchórzewski M, Snider MD, Puchowicz M, Croniger CM, Kimball SR, Pan T, Koromilas AE, Kaufman RJ, Hatzoglou M. A self-defeating anabolic program leads to β-cell apoptosis in endoplasmic reticulum stress-induced diabetes via regulation of amino acid flux. J Biol Chem. (2013) Jun 14;288(24):17202-13. PMCID:PMC 3682525

c.    Hsieh CW, Huang C, Bederman I, Yang J, Beidelschies M, Hatzoglou M, Puchowicz MA, Croniger CM. Function of phosphoenolpyruvate carboxykinase in mammary gland epithelial cells. J Lipid Res., (2011) 52(7): 1352-62. PMCID: PMC3122918

d.    Millward CA, Desantis D, Hsieh CW, Heaney JD, Pisano S, Olswang Y, Reshef L, Beidelschies M, Puchowicz MA, Croniger CM. Phosphoenolpyruvate carboxykinase (Pck1) helps regulate the triglyceride/fatty acid cycle and development of insulin resistance in mice. J Lipid Res. (2010) 51(6): 1452-63. PMCID: PMC3035508

 

3. Director of Mass Spectrometry Core Facilities: My role as a Metabolic Phenotyping and Mass Spectrometry Core Director (MMPC, MPMC) is to facilitate completion of funded projects (NIH, local). This involves assisting with study design, analysis, interpretation and manuscript submission. Moreover, I follow the success of these projects and offer continued consultation and expertise, as well as assist with submission of new proposals. With new and continued on-going collaborations, I routinely discuss standardization of new / current techniques for studying the regulation of metabolic pathways, such as for use in rodents, cell models and human of insulin resistance, obesity and altered energy expenditure. The following selected publications represent projects involving my significant contributions to outside investigator’s research.

a.    Du W, Zhang L, Brett-Morris A, Aguila B, Kerner J, Hoppel CL, Puchowicz M, Serra D, Herrero L, Rini BI, Campbell S, Welford SM. HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism. Nat Commun. (2017) Nov 8(1):1769

b.    Ruiz R, Jideonwo V, Ahn M, Surendran S, Tagliabracci VS, Hou Y, Gamble A, Kerner J, Irimia-Dominguez JM, Puchowicz MA, DePaoli-Roach A, Hoppel C, Roach P, Morral N. Sterol regulatory element-binding protein-1 (SREBP-1) is required to regulate glycogen synthesis and gluconeogenic gene expression in mouse liver. J Biol Chem. (2014) 289(9): 5510-17. PMCID: PMC3937627

c.    Krokowski D, Han J, Saikia M, Majumder M, Yuan CL, Guan BJ, Bevilacqua E, Bussolati O, Bröer S, Arvan P, Tchórzewski M, Snider MD, Puchowicz M, Croniger CM, Kimball SR, Pan T, Koromilas AE, Kaufman RJ, Hatzoglou M. A self-defeating anabolic program leads to β-cell apoptosis in endoplasmic reticulum stress-induced diabetes via regulation of amino acid flux. J Biol Chem. (2013) 288(24): 17202-13. PMCID: PMC3682525

d.    Kumashiro N, Beddow SA, Vatner DF, Majumdar SK, Cantley JL, Guebre-Egziabher F, Fat I, Guigni B, Jurczak MJ, Birkenfeld AL, Kahn M, Perler BK, Puchowicz MA, Manchem VP, Bhanot S, Still CD, Gerhard GS, Petersen KF, Cline GW, Shulman GI, Samuel VT. Targeting pyruvate carboxylase reduces gluconeogenesis and adiposity and improves insulin resistance. Diabetes (2013) 62:21831-94. PMCID:PMC3712050

e.    Ye F, Lemieux H, Hoppel CL, Hanson RW, Hakimi P, Croniger CM, Puchowicz M, Anderson VE, Fujioka H, Stavnezer E. Peroxisome proliferator-activated receptor γ (PPARγ) mediates a Ski oncogene-induced shift from glycolysis to oxidative energy metabolism. J Biol Chem. (2011) 286(46): 40013-24. PMCID: PMC3220574

 

4. Oxidative metabolism in ketotic brain. My research has focused on the use of alternate energy substrates to glucose, such as ketone bodies in brain. I have developed a rodent model (rats and mice) of diet induced ketosis and have resolved the long time question on brain’s utilization of ketone bodies during chronic ketosis. The use of stable isotopomer analysis enabled us to measure the contribution and partitioning of glucose and ketones to oxidative metabolism in vivo. We have shown that brain can utilized 40% of energy requirements as ketones following three weeks of ketogenic diet, as well as ketones are partitioned towards GABA synthesis.

a.    Tan KN, Carrasco-Pozo C, McDonald TS, Puchowicz M, Borges K. Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function. J Cereb Blood Flow Metab. (2017); 37(6):2035-48. PMCID: PMC5464699

b.    Zhang Y, Zhang S, Marin-Valencia I, Puchowicz MA. Decreased Carbon Shunting From Glucose Towards Oxidative Metabolism In Diet-Induced Ketotic Rat Brain. J Neurochem. (2015) Feb; 132(3): 301-12. PMCID:PMC4304925

c.    Zhang Y, Kuang Y, Xu K, Harris, D, Lee Z, LaManna J, Puchowicz MA. Ketosis Proportionately Spares Glucose Utilization in Brain. J Cereb Blood Flow Metab. (2013) 33(8): 1307-11. PMCID: PMC3734783

d.    Puchowicz M, Xu K, Sun X, Ivy A, Emancipator D, LaManna JC. Diet-induced ketosis increases capillary density without altered blood flow in rat brain. Am. J. Physiol. Endocrinol Metab (2007); 292: E1607-E1615.

 

5. Brain Metabolism and Ischemic Injury. The brain requires a continuous supply of energy substrate such as glucose. Under many pathophysiological conditions energy homeostasis is frequently deranged and the metabolic consequences are often irreversible and deleterious. I investigate the neuroprotective effects of ketosis and that ketone bodies are an alternate energy substrates to brain and are signaling molecules that promote preservation of brain cells during recovery from ischemia.

a.    Zhang Y, Zhang S, Marin-Valencia I, Puchowicz MA. Decreased Carbon Shunting From Glucose Towards Oxidative Metabolism In Diet-Induced Ketotic Rat Brain. J Neurochem. (2015) 132(3): 301-12. PMCID:PMC4304925

b.    Zhang Y, Kuang Y, Xu K, Harris, D, Lee Z, LaManna J, Puchowicz MA. Ketosis Proportionately Spares Glucose Utilization in Brain. (2013) J Cereb Blood Flow Metab. Aug;33(8):1307-11. PMC3734783

c.    Puchowicz MA, Zechel JL, Valerio J, Emancipator DS, Xu K, Pundik S, LaManna JC, Lust WD. Neuroprotection in diet-induced ketotic rat brain after focal ischemia. J Cereb Blood Flow Metab. (2008) 28(12): 1907-16. PMCID: PMC3621146

Click here to view all my publications.