Select Page
Dr. Inna Rabinovich-Nikitin

Dr. Inna Rabinovich-Nikitin

Principal Investigator
Women’s Heart Health and Cardiometabolic Function, Institute of Cardiovascular Sciences

Principal Investigator
Women’s Heart Health and Cardiometabolic Function, Canadian Centre for Agri-Food Research in Health and Medicine

Assistant Professor
Department of Physiology and Pathophysiology
Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba

Evelyn Wyrzykowski Family Professorship in Cardiovascular Sciences

Overview

Dr. Rabinovich-Nikitin’s laboratory is interested in the following areas of research:

  • Examining how circadian disruption during pregnancy increases the risk of complications such as preeclampsia, to identify novel diagnostic markers.
  • Exploring how maternal circadian disruption influences the long-term risk of cardiovascular disease in both the mother and the offspring.
  • Investigating the circadian factors and molecular pathways through which circadian disruption (e.g., shift work) contributes to cardiometabolic dysfunction and the development of heart failure, with an emphasis on sex-specific differences.
  • Elucidating the molecular mechanisms of atherosclerosis in endothelial cells to develop new therapeutic strategies aimed at reducing plaque buildup in blood vessels.

Why is this work important?

Circadian rhythms regulate a wide range of physiological processes, including metabolism, cardiovascular function, and pregnancy outcomes. Disruption of these rhythms due to factors like shift work, irregular sleep, or environmental stress has been increasingly linked to serious health conditions such as heart failure, atherosclerosis, and pregnancy complications.

Dr. Rabinovich-Nikitin’s research is critical for uncovering the underlying biological mechanisms that connect circadian disruption to these diseases, with a focus on sex-specific effects and intergenerational impacts. By identifying early biomarkers and therapeutic targets, this work has the potential to transform how we predict, prevent, and treat cardiometabolic and pregnancy-related disorders, ultimately improving long-term health outcomes for both individuals and future generations.

What techniques and equipment are used in this laboratory?

Dr. Rabinovich-Nikitin’s laboratory employs a multidisciplinary approach that combines molecular biology, physiology, and imaging to investigate circadian biology and cardiovascular health. Key techniques and equipment used in the lab include molecular and cellular biology techniques, animal models, cardiovascular phenotyping, microscopy and imaging, histology and tissue analysis, as well as bioinformatics and data analysis.

About Dr. Rabinovich-Nikitin

Dr. Rabinovich-Nikitin received her Ph.D. from Tel-Aviv University, followed by postdoctoral training at the University of Manitoba, where she received a fellowship from the Canadian Institute of Health Research (CIHR). 

Dr. Rabinovich-Nikitin focuses her research program on Women’s Heart Health, with the goal to advance knowledge and education toward improved diagnosis, treatment and quality of life of women with cardiac disease. 

Dr. Rabinovich-Nikitin has a track record of publishing in high-quality, peer-reviewed journals, including Circulation, Journal of Clinical Investigations, Circulation Research, Autophagy, Nature Communication, and others. She serves on the editorial board of several prestigious journals, such as Circulation Research, and has been the recipient of many prestigious research awards including the Louis N. and Arnold M. Katz Basic Science Research Prize from the American Heart Association (AHA), Martha Donovan Women’s Leadership Development Award, Ken Hughes Young Investigator Award for Medical Research, and many others.

For more information, please contact:

Inna Rabinovich-Nikitin, Ph.D.
Principal Investigator

R3042- 351 Tache Avenue
St. Boniface Hospital Research Centre
Winnipeg, Manitoba R2H 2A6

(204) 258-1251, (204) 258-1253

Circadian Rhythms

Virtually, all mammals, including humans have a circadian mechanism that controls the timing of many key physiological processes in response to a variety of environmental cues. The regulation of the molecular machinery of circadian rhythms sustains of 24 hours cycles and can differ between cell types and organisms in accordance with different metabolic requirements. The regulation of the circadian machinery begins with input from light/dark signals that are absorbed by photoreceptors in our eyes, followed by transmission through the hypothalamic master pacemaker to the rest of the body, via a combination of neural and humoral signals. Although the circadian clock mechanism outputs govern many biochemical processes as a function of the time of the day or night, the mechanism can also operate in the absence of light/dark cycles. In this case, the endogenous clocks are dynamically regulated and can be modified by other external cues, such as nutrition, temperature or environment. These signals modulate circadian regulation to promote physiological adaptations to tissue-specific metabolic needs. Disruption of the normal circadian rhythm can lead to various pathologies, including diabetes, cardiovascular disease, as well as, cardiometabolic syndrome (CMS).

Cardiometabolic syndrome

Cardiometabolic syndrome (CMS) is characterized by insulin resistance, impaired glucose tolerance, dyslipidemia, hypertension, and central adiposity. Individuals with CMS are two times more likely to die from coronary heart disease and three times more likely to have a heart attack or stroke than those who do not have the syndrome. Moreover, CMS is characterized by changes in cardiac structure and function which increase the risk for future development of heart failure (HF) among obese individuals. Notably, cardiometabolic HF is more common in women, and with higher prevalence for HF with preserved ejection fraction (HFpEF) subtype. Cardiometabolic HF is characterized by myocardial lipid accumulation, lipotoxic damage, and increased myocardial triglyceride content.

Cardiovascular health during pregnancy

Pregnancy requires significant cardiovascular adaptations to meet increased cardio-metabolic demands. These include enhanced cardiac output, plasma volume expansion, and vascular remodeling. Disruption of these physiological processes can lead to maternal cardiovascular complications and abnormal fetal cardiac development. Maternal cardiovascular health is now recognized as a critical indicator of long-term risk for heart disease later in life. Despite extensive research, the mechanistic link between circadian disruption during gestation and long-term cardiovascular disease risk remains unclear. This represents a significant knowledge gap in understanding how circadian regulation affects cardiac adaptation and recovery post-pregnancy.

Our Research Program

Disrupted circadian rhythm, such as seen in shift workers, has become extremely common in developing countries, accounting for 30% of the working force. Studies are showing that individuals who work shifts have an increased risk of developing cardiac disease. Notably, individuals who work shifts tend to increase their food intake, preferably carbohydrate-rich foods, which leads to abnormalities in lipid and triglycerides levels, increase in glucose levels and high blood pressure. Many population studies support these observations by showing that circadian disruption, such as seen in shift work, is closely associated with increased risk for CMS due to circadian misalignments caused by chronically irregular sleeping and eating times. Similarly, maternal shift work is also known as a risk factor for adverse pregnancy outcomes both for the mother and the offspring.

Our research program focuses on discovering novel key genes and networks that are associated with both circadian rhythms and metabolic function in females, toward developing innovative therapeutic strategies to treat cardiometabolic dysfunction. Therefore, we focus on understanding how disruption to circadian machinery provokes cardiometabolic dysfunction that leads to the development of HF in response to CMS in females. Another important aspect of our research program is to explore how disrupted circadian rhythm during pregnancy adversely affects cardiac function and fetal development toward better understanding of how to mitigate the future increased risk for heart in both the mother and the offspring.

* Last three years

  1. Flores RC, Yaffe R, Nhunzwi MM, Nguyen H, Rabinovich-Nikitin I. Maternal shift work during pregnancy and cardiovascular health impacts on mother and offspring. J Mol Cell Cardiol. 199:126-132. 2025.
  2. Zhang H, Singal PK, Ravandi A, Rabinovich-Nikitin I. Sex-Specific Differences in the Pathophysiology of Hypertension. Biomolecules. 18;15(1):143. 2025.
  3. Bhullar SK, Thingnam R, Nematisouldaragh D, Crandall M, Rabinovich-Nikitin I, Willerth SM, Ramkrishna S, Kirshenbaum LA. Living Nanofibers-Enabled Cardiac Patches for Myocardial Injury. JACC: Basic to Translational Science. 10 (2) 227–240. 2025.
  4. Narous M, Nugent Z, Rabinovich-Nikitin I, Kirshenbaum LA, Bernstein CN. Cardiac arrhythmia in patients with inflammatory bowel disease: a retrospective, population-based cohort study in Manitoba, Canada. BMJ open. 15(3):e097687. 2025
  5. Nematisouldaragh D, Eryn Kirshenbaum, Michael Uzonna, Lorrie Kirshenbaum, Rabinovich-Nikitin I. The Role of Retinoic-Acid-Related Orphan Receptor (RORs) in Cellular Homeostasis. Int. J. Mol. Sci. 25(21):11340. 2024
  6. Rabinovich-Nikitin I, Crandall M, and Kirshenbaum LA. Circadian-Regulated GR Signaling Mediates Morning Arrhythmias. Circ Res. 10;134(10):1327-1329. 2024.
  7. Guberman M, Dhingra R, Cross J, Margulets V, Gang H, Rabinovich-Nikitin I*, Kirshenbaum LA*.IKKβ stabilizes Mitofusin 2 and suppresses doxorubicin cardiomyopathy. Cardiovasc Res. cvad145. 2024.
  8. Nematisouldaragh D, Nguyen H, Rabinovich-Nikitin I. Agonists, inverse agonists, and antagonists as therapeutic approaches to manipulate retinoic acid-related orphan receptors. Can J Physiol Pharmacol. 102(11):620-633. 2024.
  9. Rabinovich-Nikitin I, Shuangbo L, Kirshenbaum LA. Sex-specific considerations in cardiovascular drug therapy. Can J Physiol Pharmacol. 102(9):523-529. 2024.
  10. Bhullar SK, Kirshenbaum LA, Rabinovich-Nikitin I. Oral hormonal contraceptives and cardiovascular risks in females. Can J Physiol Pharmacol. 102(10):572-584. 2024.
  11. Rabinovich-Nikitin I, Liu S, Kirshenbaum L. Introduction-Unveiling gender disparity in heart disease. Can J Physiol Pharmacol. 102(8):430. 2024.
  12. Kirshenbaum E, Nguyen H, Margulets V, Crandall M, Nematisouldaragh D, Rabinovich-Nikitin I. Retinoic acid-related orphan receptors regulate autophagy and cell survival in cardiac myocytes during hypoxic stress. J Cardiovasc Aging.3:40. 2023.
  13. Rabinovich-Nikitin I and Kirshenbaum LA. BMAL1 regulates cell cycle progression and angiogenesis of endothelial cells. Cardiovasc Res. cvad103. 2023.
  14. Rabinovich-Nikitin I and Kirshenbaum LA. Circadian-Regulated Cardiac Metabolism Involves Transcription Factor E4BP4. JACC: Basic to Translational Science. 8(9)1157–1159. 2023.
  15. Rabinovich-Nikitin I and Kirshenbaum LA. Autophagy, clock genes and cardiovascular disease. Can J Cardiol. 29:S0828-282X(23)01639-2. 2023.
  16. Rabinovich-Nikitin I, Crandall M, and Kirshenbaum LA. Circadian Regulation of Genetic and Hormonal Risk Factors of Cardiovascular Disease in Women. Can J Physiol Pharmacol. 101(1):1-7. 2023.
  17. Rabinovich-Nikitin I, Kirshenbaum LA. Mef2 regulated cardiac hypertrophy and heart failure in hypertension. Trends Cardiovasc Med. S1050-1738(22)00011-1. 2023.
  18. Rabinovich-Nikitin I*, Blant A*, Dhingra R, Kirshenbaum LA and Czubryt MP. NF-κB p65 Attenuates Cardiomyocyte PGC-1α Expression in Hypoxia. Cells. 11(14), 2193. 2022.
  19. Rabinovich-Nikitin I, and Kirshenbaum LA. Rev-erb-mediated Regulation of Cardiac Metabolism in the Obesity Paradox. Circulation. 145(6):465-468.
  20. Rabinovich-Nikitin I, Love M, Kirshenbaum LA. Intersection of autophagy regulation and circadian rhythms in the heart. Biochim Biophys Acta Mol Basis Dis. 1868(4):166354. 2022.
  21. Gavriel Y, Rabinovich-Nikitin I, Solomon B. Inhibition of CXCR4/CXCL12 signaling: a translational perspective for Alzheimer’s disease treatment. Neural Regen Res. 17(1):108-109. 2022.
  22. Zacharioudakis E, Agianian B, Kumar V, Biris N, Garner T, Rabinovich-Nikitin I, Ouchida AT, Margulets V, Nordstrom L, Riley J, Dolgalev I, Chen Y, Wittig A, Pekson R, Tsirigos A, Kirshenbaum LA, Kitsis R, Gavathiotis E. Modulating mitofusins to control mitochondrial function and signaling. Nat Commun. 13(1):3775. 2022.
  23. Dhingra R, Rabinovich-Nikitin I, Rothman S, Guberman M, Gang H, Margulets V, Jassal DS, Alagarsamy KN, Dhingra S, Ripoll CV, Billia F, Diwan A, Javaheri A and Kirshenbaum LA. Proteasomal Degradation of TRAF2 Mediates Mitochondrial Dysfunction in Doxorubicin-Cardiomyopathy. Circulation. 146(12):934-954. 2022.
  24. Rabinovich-Nikitin I, Kirshenbaum LA. Circadian regulated control of myocardial ischemia-reperfusion injury. Trends Cardiovasc Med. S1050-1738(22)00120-7. 2022.

Book chapters:

  1. Bhullar SK, Thingnam R, Rabinovich-Nikitin I, Kirshenbaum LA. Doxorubicin Induced Mitochondrial Dysfunction and Cardiotoxicity. Cardiovascular Toxicity: Incidence, Pathogenesis and Treatment Strategies. Springer Nature Scientific publishing group. 2025.
  2. Huong Nguyen, Breno Lintz, Rabinovich-Nikitin I. The effects of lipophilic vitamins on women’s heart health. Pram Tappia. Lipophilic vitamins in health and disease. Springer Nature Scientific publishing group: vol. 28: 73-84. 2024.
  3. Huong Nguyen, Kirshenbaum LA, Rabinovich-Nikitin I. The need for Women’s Heart Health Research. Lorrie A Kirshenbaum and Inna Rabinovich-Nikitin. Biology of Women’s Heart Health. Springer Nature Scientific publishing group: vol. 19: 1-8. 2023.
  4. Crandall M, Rabinovich-Nikitin I, Kirshenbaum LA. Molecular Basis of the Circadian Mechanism in Women. Lorrie A Kirshenbaum and Inna Rabinovich-Nikitin. Biology of Women’s Heart Health. Springer Nature Scientific publishing group: vol. 19: 205-217. 2023.

* Last three years

2025                Ken Hughes Young Investigator Award for Medical Research

2024                Women in Health Sciences Award, Magnificent Women’s Awards

2023                Buddha Dawn Early Career Award, International Academy of Cardiovascular Sciences (IACS)

2023                The Litsa Kranias ECI Leadership Award, International Society for Heart Research (ISHR)

2023                Outstanding Early Career Investigator Award, NIH Progenitor Cell Translational Consortium

2022                Louis N. and Arnold M. Katz Basic Science Research Prize for Early Career Investigators, American Heart Association (AHA)

2022                ISHR International Best Poster Award, International Society for Heart Research (ISHR)

2022                ISHR ECI Travel Award, International Society for Heart Research (ISHR)

  • Canadian Institute of Health Research (CIHR)
  • Heart and Stroke Foundation
  • Research Manitoba
  • St. Boniface Hospital Foundation
  • Canadian Space Agency (CSA)   

     

    Contact Dr. Rabinovich-Nikitin

    Life In the Lab