Baba Lab
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About
The focus of our laboratory is to understand the mechanisms that regulate cardiac and skeletal muscle function under physiological and pathological conditions and translate the findings in population suffering from cardiovascular diseases.
During heart failure there is excessive generation of toxic lipid peroxidation products, and a shift in glucose utilization in the heart and skeletal muscle. The toxic aldehydes react with proteins forming damage associated molecular patterns (DAMPS) and trigger inflammation. Our goal is to identify DAMPs, their contribution in inciting inflammation and diminish their toxicity.
In the heart and skeletal muscle there are present histidyl dipeptides, such as carnosine and anserine, synthesized via the enzyme carnosine synthase (CARNS, encoded by Carns) that exhibit multiple properties, such as scavenging reactive aldehydes, binding with ADAMPs and pH buffering. Leveraging from these multiple abilities and altering the levels of histidyl dipeptides in the heart and skeletal muscle, we are studying how these dipeptides influence the immunogenicity of DAMPs and skeletal muscle metabolism during heart failure.
Previously we showed supplementation of carnosine improves blood flow in the ischemic limb and removes toxic aldehydes from humans. Currently we are performing a NIH funded phase II clinical trial to examine the effect of carnosine on the walking ability of peripheral arterial disease patients.
Key Research Areas
- Identify and diminish the immunogenicity of triggers leading to heart failure reduced and preserved ejection fraction.
- Elucidate the mechanisms of exercise intolerance during heart failure.
Current Projects
- Identify DAMPs generated during heart failure with reduced and preserved ejection fraction and their contribution in eliciting innate and adaptive immune responses.
- Effects of carnosine intervention on the walking ability of peripheral arterial disease patients.
- How shift in skeletal muscle metabolism influences exercise capacity during heart failure?
Team
Shahid Baba, Ph.D.
Director. Baba's main research is focused in examining the metabolic role of aldo-keto reductases (AKRs), in metabolizing different advanced glycation end products (AGEs) precursors and advanced lipoxidation products (ALEs).
Mamata Chaudhari
Ph.D. student, Department of Physiology. Studying the role of histidyl dipeptides in heart failure induced muscle wasting. Mamata is funded by AHA Predoctoral Fellowship (2025-2027).
Benjamin (Ben) Doelling
Ph.D student, Department of Biochemistry. Identifying and diminishing the immunogenicity of inflammation in failing hearts. Ben is funded by AHA Predoctoral Fellowship (2025-2027).
Our Work
Chaudhari M, Zelko I, Lorkiewicz P, Hoetker D, Doelling B, Brittian K, Bhatnagar A, Srivastava S, Baba SP. Metabolic pathways for removing reactive aldehydes are diminished in atrophic muscle during heart failure. Skeletal muscle. 2024. PMID:38045249
Baba SP, Amraotkar AR, Hoetker D, Gao H, Gomes D, Zhao J, Wempe MF, Rice PJ, DeFilippis AP, Rai SN, Pope CA 3rd, Bhatnagar A, O'Toole TE. Evaluation of supplementary carnosine accumulation and distribution: an intial analysis of participants in the nucleophilic defense against PM toxicity (NEAT) clinical trial. Amino acids. 2024. PMID:39215872
- Amraotkar AR, Hoetker D, Negahdar MJ, Ng CK, Lorkiewicz P, Owolabi US, Baba SP, Bhatnagar A, O'Toole TE.Comparative evaluation of different modalities for measuring invivo carnosine levels.PLos One. 2024, PMID:38536838
- Posa DK, Miller J, Hoetker D, Ramage MI, Hong G, Zhao J, Doelling B, Bhatnagar A, Wigmore SJ, Skipworth, RJE, Baba SP. Skeletal muscle analysis of cancer patients reveals a potential role for carnosine in muscle wasting, Journal of Cachexia Sarcopenia Muscle. 2023. PMID:37199284
Spaas J, Van der Stede T, de Jager S, van de Waterweg Berends A, Tiane A, Baelde H, Baba SP, Eckhardt M, Wolfs E, Vanmierlo T, Hellings N, Eijnde BO, Derave W. Carnosine synthase deficiency aggravates neuroinflammation in multiple sclerosis. Prog Neurobiol. 2023. PMID 37774767
Feehan J, Hariharan R, Buckenham T, Handley C, Bhatnagar A, Baba SP, de Courten B. Carnosine as a potential therapeutic for the management of peripheral vascular disease. Nutr. Metab. Cardiovas Dis. 2022. PMID: 35797388
Dwenger MM, Raph SM, Baba SP, Moore JB, Nystoriak MA. Diversification of Potassium currents in excitable cells via Kvb proteins. Cells. 2022. PMID 35883673.
Yan, K, Zhanglong M, Zhao JJ, Prodhan, MAI, Obal D, Katragadda K, Hoetker D, Posa DK, He L, Yin X, Shah J, Lorkiewicz PK, Zhang X, Li S, Bhatnagar A, and Baba SP. Integrated multilayer omics reveals genomic, proteomic, and metabolic influences of histidyl dipeptides on the heart. JAHA. 2022: PMID 35730646.
Spaas J, Franssen WMA, Keytsman C, Blancquaert L, Vanmierlo T, Bogie J, Broux B, Hellings N, van Horssen J, Posa DK, Hoetker D, Baba SP, Derave W, Eijnde BO. Carnosine quenches the reactive carbonyl acrolein in the central nervous system and attenuates autoimmune neuroinflammation.J Neuroinflammation. 2021. PMID: 34740381
Posa DK, Baba SP. Intracellular pH buffering of the skeletal muscle in the milieu of Insulin signaling. Nutrients. 2020. PMID:32977552
Baba SP, Hellmann J, Bhatnagar A, Carter K, Vanhoover A, Caruso J. Space flight diet induced deficiency and response to gravity-free resistive exercise. Nutrients. 2020. PMID: 32796546.
O'Toole TE, Li X, Riggs DW, Hoetker DJ, Yeager R, Lorkiewicz P, Baba SP, Cooper NGF, Bhatnagar A. Urinary levels of the acrolein conjugates of carnosine are associated with inhaled toxicant. Inhal Toxicol. 2020. PMID:33179563.
O'Toole TE, Amraotkar AA, DeFilippis AP, Rai SN, Keith RJ, Baba SP, Lorkiewicz P, Crandell CE, Pariser GL, Wingard CJ, Pope Iii CA, Bhatnagar A. Protocol to assess the efficacy of carnosine supplementation in mitigating the adverse cardiovascular responses to particulate matter (PM) exposure: the nucleophilic defense against PM toxicity (NEAT) trial. BMJ Open. 2020. PMID:33372072
Zhao JJ, Conklin DJ, Guo Y, Zhang X, Obal D, Guo L, Jagatheesan G, Katragadda K, He L, Yin X, Prodhan IAM, Shah J, Hoetker D, Kumar A, Kumar V, Wempe MF, Bhatnagar A and Baba SP. Cardio-specific overexpression of ATPGD1 increases histidine dipeptide levels and prevents myocardial ischemia-reperfusion injury. JAHA. 2020. PMID:32515247.
Everaert I, He J, Hanssens M, Stautemas J, Bakker K, Albrecht T, Zhang S, Van der Stede T, Vanhove K, Hoetker D, Howsam M, Tessier FJ, Yard B, Baba SP, Baelde HJ, Derave W. Carnosinase-1 overexpression, but not aerobic exercise training, affects the development of diabetic nephrophathy in BTBR ob/ob mice. Am J Physiol Renal Physiol. 2020. PMID 32150446
Boakye AA, Zhang D, Guo L, Zheng Y, Hoetker D, Zhao J, Posa DK, Ng CK, Zheng H, Kumar A, Kumar V, Wempe MF, Bhatnagar A, Conklin DJ, Baba SP. Carnosine supplementation enhances post ischemic hindlimb revascularization. Frontiers Physiology. 2019. PMID: 31312142
Hoetker D, Chung W, Zhang D, Zhao J, Schmidtke VK, Riggs DW, Derave W, Bhatnagar A, Bishop DJ, Baba SP. Exercise alters and β-alanine combined with exercise augments histidyl dipeptide levels and scavenges lipid peroxidation products in human skeletal muscle. J Appl Physiol. 2018. PMID:30335580.
Zhao J, Posa DK, Kumar V, Hoetker D, Kumar A, Ganesan S, Riggs DW, Bhatnagar A, Wempe MF, Baba SP. Carnosine protects cardiac myocytes against lipid peroxidation products. Amino Acids. 2019. PMID:30449006
Derave W, De Courten B, Baba SP. An update on carnosine and anserine research. Amino Acids. 2019. PMID:30694382.
- Zhang D, Bhatnagar A, Baba SP. Inhibition of aldose reductase activity stimulates starvation induced autophagy and clears aldehyde protein adducts. Chemico-Biological Interactions. 2019. PMID: 30998906
Past Members
Postdoctoral Fellows
2015-2020 Dr. Jing Jing Zhao
2013-2017 Deqing Zhang
Graduate students
2012-2017: Adjoa Boakaye, Dept. of Biochemistry. University of Louisville
2014-2015: Maartin Missine, Dept. of Movement and Sports Sciences, University of Ghent, Belgium.
2020-2023: Jan SPAAS, Dept. of Movement and Sports Sciences, University of Ghent Belgium
Undergraduate students
2023: Junaid Shahzad. Dept. of Physiology. University of Louisville
2022: Ibrahim Jouja, Emory University
2015: Hayley Scholl, University of Louisville
2016: Faith Page, Earlham College, Indiana
2018: Cyrus Buckman, Earlham College, Indiana
2018: Smirthy Ganesan, Earlham College, Indiana