Professor and Head,
Department of Biochemistry,
Christian Medical College,
Bagayam, Vellore, Tamil Nadu, India – 632002
Phone: +91-416-2284267 (office), +91-416-2284458 (lab)
Degree Period Institution University
MBBS 1997-2002 KIMS, Bangalore RGUHS, Bangalore, Karnataka
MD (Biochemistry) 2004-2007 Christian Medical College, Vellore TNMGRMU, Chennai, Tamil Nadu
DNB (Biochemistry) 2007 Christian Medical College, Vellore NBE, New Delhi
Ph.D. (Biochemistry) 2019 Christian Medical College, Vellore TNMGRMU, Chennai, Tamil Nadu
The broad area of my research is in the field of iron metabolism. Iron is a transition metal that plays a critical role in a variety of physiological processes, such as growth and proliferation, oxygen transport, enzyme activity etc. Our understanding of the regulation of systemic and cellular iron homeostasis has increased exponentially over the past couple of decades. At the same time, it is also being recognized that dysregulation of iron homeostasis is involved in the pathogenesis of several diseases as well. In my research, I am currently focused on studying the role of iron in the pathogenesis of diabetes mellitus and chronic non-healing ulcers.
Iron and diabetes mellitus
A mild-to-moderate increase in body iron stores is known to be associated with diabetes mellitus. A few studies have suggested that an increase in beta-cell iron levels may adversely affect its function and potentially increase the risk of beta cell failure. However, very little is known about the underlying mechanisms involved. Planned and on-going work in the lab is aimed at studying this at the molecular and functional level.
Using animal models of dietary and genetic iron overload, we are investigating the effect of iron on beta cells isolated from the pancreas and cultured ex vivo. In our studies involving humans, the effects of oral iron supplementation on insulin secretion kinetics and glucose tolerance is being evaluated. These studies will shed light on the effect of iron on beta-cell function. Overall, we hope to understand whether increased body iron is a risk factor for diabetes mellitus, especially in those who are genetically pre-disposed to it.
Role of iron in wound healing
There is an urgent need to develop new and effective therapeutic strategies to promote wound healing in patients with chronic non-healing ulcers. Iron is essential for normal wound healing. However, iron tends to accumulate in chronic wounds, and it is thought to impair the healing process in this setting. The underlying mechanisms involved are, however, not clear.
Using animal models of cutaneous wounds, we aim to investigate the role of iron as a factor that inhibits the process of wound healing. In collaboration with the Department of Physical Medicine and Rehabilitation at CMC, Vellore, we have initiated translational research work which will look at the pathophysiological role of iron overload that is often seen in pressure ulcers, a common cause of chronic non-healing ulcers. In addition, our work in this area is also focussed on evaluating iron chelation as a novel therapeutic modality to accelerate healing in such wounds.
Past research projects
A number of epidemiological studies suggest a strong association between insulin resistance and increased body iron stores. However, whether increased body iron is a cause or consequence of insulin resistance is not known. In order to study the dysregulation of iron homeostasis associated with insulin resistance, I was awarded an Early Career Fellowship by the Wellcome Trust-DBT India Alliance (2012-16). The India Alliance-funded work has helped elucidate the interactions between iron homeostasis and insulin sensitivity and has resulted in several publications (please see publication list).
In the past, I have been awarded a grant under the Rapid Grant for Young Investigators (RGYI) scheme of the Department of Biotechnology (DBT), Govt. of India (2008-2011), to study the role of heme oxygenase – 1 (HO-1) in the pathogenesis of iron overload associated with alcoholic liver disease. It has been reported that chronic alcoholism is associated with increased liver iron stores and that this may play a role in the pathogenesis of liver damage associated with chronic alcohol intake. However, the cause(s) for the iron accumulation in the liver in this condition is/are not entirely clear. Work on this project was aimed at elucidating the mechanisms that may be involved.
TEACHING AND TRAINING
I teach undergraduate medical and nursing students. For the first year MBBS students, I teach the modules on molecular biology, water and electrolyte balance, heme metabolism, immunology, liver function tests and integration of metabolism. In my teaching, I explore innovative methods to help students understand the importance of a sound foundation in the basic medical sciences for their further development as clinicians. In this connection, I am especially interested in the use of electronic resources (e-learning) as an aid to help students learn the clinical and applied aspects of Biochemistry more effectively. I also have a special interest in teaching undergraduate and post-graduate students the basics of ethical academic/research writing.
I am involved in the training of MD (Biochemistry) students. I am the coordinator of the postgraduate training programme. I serve as a resource person for weekly post-graduate seminars and journal clubs. In addition, I am involved in the supervision (as co-guide) of research work undertaken by postgraduate students as part of their dissertation work.
RESEARCH GRANTS HELD
As Principal Investigator or co-principal investigator:
Core Research Grant (CRG) awarded by Science and Engineering Research Board (SERB) for the project "Effect of iron on pancreatic beta cell function and glucose tolerance in pregnancy (Iron and GDM)" - 2023-2025.
Christian Medical College Fluid Research Grant for the project "Effect of iron on insulin secretion and insulin sensitivity during pregnancy in mice"
Christian Medical College Fluid Research Grant for the project “Role of iron in wound healing”
Christian Medical College Fluid Research Grant for the project “Effect of hepatic steatosis on iron homeostasis in the liver”
Christian Medical College Fluid Research Grant for the project “Effect of iron on pancreatic islet function in a mouse model of dietary iron overload”
Wellcome Trust-DBT India Alliance - Early Career Fellowship for the project entitled “Why does iron overload associated with insulin resistance occur?” (2012 - 2016)
Department of Biotechnology (DBT), Government of India - Rapid Grant for Young Investigators (RGYI) for the project titled “Is activation of heme oxygenase-1 involved in iron accumulation in alcoholic liver disease?” (2008 – 2012)
Christian Medical College Fluid Research Grant for the project “Acute effect of a single dose of oral iron on pancreatic beta cell function in healthy individuals: a quasi-experimental single arm before-and-after (pre-post) study”
Christian Medical College Fluid Research Grant for the project “How aware are medical students regarding issues of plagiarism?” (2011-2012)
Christian Medical College Fluid Research Grant for the project “How aware are medical post-graduate students in CMC of issues related to plagiarism in research?” (2012-2013)
Christian Medical College Fluid Research Grant for the project “Assessment of zinc as an agent to prevent indomethacin- induced renal damage” (2004 – 2007)
Project title: Oxidative stress and iron levels in follicular fluid of infertile women with endometrioma undergoing ART. Funding agency: CMC Fluid Research Funds (PI: Dr. Monica Peter)
Project title: Effect of iron on ferroptosis in granulosa cells: implications for fertility in women with endometriosis. Funding agency: CMC Fluid Research Funds (PI: Dr. Monica Peter)
Project title: Effect of short-term (4 weeks) low-calorie diet on beta-cell function in overweight normoglycemic subjects. Funding agency: CMC Fluid Research Funds (PI: Dr. Padmanaban V)
Project title: Is alternate day oral iron more effective in improving iron status of young Indian women than daily doses? Principal Investigator: Dr. Molly Jacob. Funding agency: GCRF UCL Internal Small Grants Call of University College, London, UK in partnership with the Overseas Development Agency (ODA) in the UK (PI: Dr. Molly Jacob)
Project title: Iron supply in pregnancy – a model to establish research exchange, high level education and cooperation with India. Principal Investigator: Dr. Molly Jacob. Funding agency: Deutscher Academischer Austauschdienst (DAAD) - German Academic Exchange Service. (PI: Dr. Molly Jacob)
Project title: "Does an iron overloaded state predispose to an earlier development of insulin resistance in response to a high-fat diet (HFD)?" Principal Investigator: Dr. Molly Jacob; Funding agency: Science and Engineering Research Board (SERB), Department of Science and Technology (DST), New Delhi. (PI: Dr. Molly Jacob)
Project title: "Why do patients with Helicobacter pylori infection develop iron-deficiency anemia?" Principal Investigator: Dr. Molly Jacob; Funding agency: Indian Council of Medical Research (ICMR), New Delhi. (PI: Dr. Molly Jacob)
Project title: "Iron overload in alcoholic liver disease: why does it occur?" Principal Investigator: Dr. Molly Jacob; Funding agency: Indian Council of Medical Research (ICMR), New Delhi. (PI: Dr. Molly Jacob)
Varghese J*, Peter M, Kamath MS. Oogenesis Arrest Prior to Birth: A Trade-off between Possible Evolutionary Advantages and Age-Related Oocyte Dysfunction? Fertility & Reproduction. 2021 Sep 28;3(03):55-7. – * corresponding author
Venkatesan P, Varghese J*, Arthi TS, James JV, Anura A, Prasad J, Jacob M. Evidence of dysregulated iron homeostasis in newly diagnosed diabetics, but not in pre-diabetics. J Diabetes Complications. 2021 Jun 19:107977. doi: 10.1016/j.jdiacomp.2021.107977. (IF: 2.852) * co-first author
Varghese J, James JV, Narayanasamy M, Anand R, Rebekah G, Ramakrishna B, Nellickal AJ, and Jacob M. Development of insulin resistance preceded major changes in iron homeostasis in mice fed a high-fat diet (2020). J Nutr Biochem. 2020 Jun 2;84:108441 (IF: 4.490)
James JV, Varghese J*, Mckie AT, Vaulont S, Jacob M. Enhanced insulin signaling and its downstream effects in iron-overloaded primary hepatocytes from hepcidin knock-out mice. Biochim Biophys Acta Mol Cell Res. 2019 Dec 5;:118621. (IF: 4.739) *co-first author
Varghese J, Varghese James J, Karthikeyan M, Rasalkar K, Raghavan R, Sukumaran A, Premkumar PS, Eapen CE, Jacob M. Iron homeostasis is dysregulated, but the iron-hepcidin axis is functional, in chronic liver disease. J Trace Elem Med Biol. 2019 Nov 28;58:126442. (IF: 2.895)
Varghese J, James J, Vaulont S, Mckie A, Jacob M (2018). Increased intracellular iron in mouse primary hepatocytes in vitro causes activation of the Akt pathway but decreases its response to insulin. Biochim Biophys Acta Gen Subj. 2018 Sep;1862(9):1870-1882. (IF: 3.681)
Varghese J, James JV, Sagi S, Sukumaran A, Ramakrishna B and Jacob M (2016). Decreased hepatic iron in response to alcohol may contribute to alcohol-induced suppression of hepcidin. Br. J Nutr 2016 Jun;115(11):1978-86 (IF: 3.657)
Nagappan AS, Varghese J, James JV, Jacob M. Indomethacin induces endoplasmic reticulum stress, but not apoptosis, in the rat kidney. Eur J Pharmacol. 2015 Aug 15;761:199-205 (IF: 3.040)
Varghese J, and Jacob M. Do medical students require education on issues related to plagiarism? Indian Journal of Medical Ethics 2015 Apr-Jun;12(2):82-7
Nagappan AS, Varghese J, Pranesh GT, Jeyaseelan V, Jacob M. Indomethacin inhibits activation of endothelial nitric oxide synthase in the rat kidney: Possible role of this effect in the pathogenesis of indomethacin-induced renal damage. Chem Biol Interact. 2014 Aug 8;221C:77-87. (IF: 3.296)
Patel N, Varghese J, Masaratana P, Latunde-Dada GO, Jacob M, Simpson RJ, McKie AT. The transcription factor ATOH8 is regulated by erythropoietic activity and regulates HAMP transcription and cellular pSMAD1,5,8 levels. Br J Haematol. 2014 Feb;164(4):586-96. (IF: 5.128)
Varghese J, Faith M and Jacob M. Impact of e-resources on learning in biochemistry: first-year medical students' perceptions (2012). BMC Med Edu 2012 May 16;12:21. (IF: 1.511)
Sukumaran A, Varghese J, Tamilselvan J, Jeyaseelan V, Mani T, Simpson RJ, McKie AT, Jacob M Effects of acute and chronic inflammation on proteins involved in duodenal iron absorption in mice: a time-course study. Br. J Nutr. 2012 Feb 24:1-8 (IF: 3.657)
Varghese J, Faith M, Jacob M. (2009) Zinc prevents indomethacin-induced renal damage in rats by ameliorating oxidative stress and mitochondrial dysfunction. Eur J Pharmacol. 2009 Jul 1;614(1-3):114-21. doi: 10.1016/j.ejphar.2009.04.053. (IF: 3.040)
Chapters in books
Senior Training Fellowship (STF - 2023) to train at the University of Oxford, UK for a period of 8 weeks.
CDSA Research Training Fellowship (2018) to train at the University of Girona, Spain (Prof. Fernandez-Real’s lab) for a period of 6 weeks.
Early Career Fellowship by the Wellcome Trust-DBT India Alliance (2012-2016) to study the role of iron overload in the pathogenesis of insulin resistance. This included an 18-month stint in the laboratory of Prof. Andrew Mckie at King’s College, London.
Junior Medical Faculty Training Fellowship (JMFTF - 2009) to train at the University of Nebraska, Omaha, Nebraska, USA (Prof. Harrison-Findik’s lab), from November to December 2009.
First prize (oral presentation, faculty members - Basic Science category) at the Annual Research Day in Christian Medical College, Vellore, in 2013, 2014, 2015, and 2018
Second prize (oral presentation, faculty members - Basic Science category) at the Annual Research Day in Christian Medical College, Vellore, in 2021
Third prize (oral presentation, faculty members - Basic Science category) at the Annual Research Day in Christian Medical College, Vellore, in 2017
Drs. Molly and Thomas Bhanu Award for the Best Teacher (2012) - Christian Medical College, Vellore