Joe Varghese

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

RESEARCH INTERESTS

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 in general and gestational diabetes mellitus in particular, and chronic non-healing ulcers.

Iron supplementation and gestational diabetes mellitus

All pregnant women in India are routinely prescribed oral iron supplements, as part of the Anemia Mukt Bharat (AMB) program. In women with iron-deficiency anemia, the benefits of iron supplementation during pregnancy for both the mother and child are very clear. Since the prevalence of anemia among pregnant women is unacceptably high (52.2% as per NFHS-5 data), the current strategy of universal iron supplementation to all pregnant women (irrespective of anemia status) makes logistical sense. Nevertheless, in non-anemic pregnant women, the benefits of iron supplementation vis-à-vis associated risks have not been studied adequately. Studies have suggested that iron may impair insulin secretion, thus increasing the risk of gestational diabetes mellitus (GDM). It is therefore important to generate evidence on the safety of the current strategy of iron supplementation in this sub-group (non-anemic pregnant women) of Indian women.

To address this, we are carrying out a randomized, parallel-group, double-blinded clinical trial funded by the ICMR, where the incidence of GDM in non-anemic primigravidae who receive oral iron supplementation of 60 mg of elemental iron per day (as per AMB program) will be compared to that in those who receive 30 mg of elemental iron/day for a period of 12 weeks in the second trimester of pregnancy. In addition, we plan to study kinetics of insulin secretion during the oral glucose tolerance test (OGTT) and levels of circulating unmethylated INS DNA (a sensitive and specific marker of beta-cell damage) in these two groups of women.

Effect of iron on insulin secretion and insulin resistance

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, both in humans and in animal models. In a related project funded by SERB, we are looking at the relationship between gestational diabetes mellitus and circulating levels of non-transferrin bound iron (NTBI). We hypothesize that elevated levels of NTBI may be related to impaired beta-cell function in pregnant women with GDM.

I the past I have received the Early Career Fellowship from the Wellcome Trust-DBT India Alliance, spanning from 2012 to 2016. The research funded by the India Alliance has significantly contributed to understanding the connections between iron homeostasis and insulin resistance, leading to the publication of multiple research papers (refer to the publication list for details). 

Role of iron in wound healing and the pathogenesis of pressure ulcers

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.

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 focused on evaluating iron chelation as a novel therapeutic modality to accelerate healing in such wounds.

Role of iron in the pathogenesis of metabolic dysfunction-associated steatotic liver disease 

It has been shown that iron may play a role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease or MASLD (earlier called non-alcoholic fatty liver disease or NAFLD). On-going work in this area is looking at the underlying molecular mechanisms. In particular, we are interested in studying whether iron chelation can significantly retard the development and progression of MASLD.

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. 

TEACHING AND TRAINING

Undergraduate training

I teach undergraduate medical, AHS 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.

Postgraduate training

I am involved in the training of MD (Biochemistry) students. I serve as a resource person for faculty lectures, weekly post-graduate seminars and journal clubs. In addition, I am involved in the supervision of research work undertaken by postgraduate students as part of their dissertation work. 

RESEARCH GRANTS HELD

As Principal Investigator or co-principal investigator:

Ongoing extramural:

1. ICMR – Investigator Initiated Projects – Intermediate Grant for the project titled, "Iron supplementation during pregnancy and the risk of gestational diabetes mellitus - a randomized, parallel-group, double-blinded clinical trial" (2024 - 2028)

2. 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.

Ongoing intramural:

1. Christian Medical College Fluid Research Grant for the project "Effect of iron on insulin secretion and insulin sensitivity during pregnancy in mice" 

2. Christian Medical College Fluid Research Grant for the project “Role of iron in wound healing” 

3. Christian Medical College Fluid Research Grant for the project “Effect of hepatic steatosis on iron homeostasis in the liver” 

4. Christian Medical College Fluid Research Grant for the project “Effect of iron on pancreatic islet function in a mouse model of dietary iron overload” 

Past extramural:

1. Wellcome Trust-DBT India Alliance - Early Career Fellowship for the project entitled “Why does iron overload associated with insulin resistance occur?” (2012 - 2016)

2. 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) 

Past intramural:

1. 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” 

2. Christian Medical College Fluid Research Grant for the project “How aware are medical students regarding issues of plagiarism?” (2011-2012)

3. 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) 

4. Christian Medical College Fluid Research Grant for the project “Assessment of zinc as an agent to prevent indomethacin- induced renal damage” (2004 – 2007) 

As Co-investigator:

Ongoing intramural:

1. Project title: Estimation of serum non-transferrin bound iron (NTBI) levels by an inductively coupled plasma mass spectrometry (ICP-MS) based assay: assay validation and NTBI estimation in cohorts of beta-thalassemia major patients undergoing bone marrow transplantation. Funding agency: CMC intramural funds (PI: Dr. Padmanaban V)

2. 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)

3. 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)

4. 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)

5. Project title: The bacterial microbiome in pressure ulcers: a descriptive study (2021 – 2023). Principal Investigator: Dr. Jane Elizabeth Sajan. Funding agency: Christian Medical College Fluid Research Major Grant

Ongoing extramural:

6. 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)

7. 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)

8. Project title: Iron uptake and handling by the placenta – how does this occur and is it affected by inflammation? Principal Investigator: Molly Jacob is supervisor, on Young Scientist Scheme (YSS) (Young Scientist: Nikhitha Mariya John). Funding agency: Department of Health Research (DHR), New Delhi

9. Project title: Iron homeostasis in macrophages: is it involved in the development of inflammation in adipose tissue and subsequent insulin resistance? Principal Investigator: Molly Jacob is supervisor, on Woman Scientist Scheme (WSS) (Woman Scientist: Anji Anura). Funding agency: Department of Health Research (DHR), New Delhi

Past extramural:

10. 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)

11. 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)

12. 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)

PUBLICATIONS

Research papers:

1. Ramasamy J, Jagadish C, Sukumaran A, Varghese J, Mani T, Joseph AJ, Simon EG, Jacob M. Low Serum Hepcidin Levels in Patients with Ulcerative Colitis - Implications for Treatment of Co-existent Iron-Deficiency Anemia. Inflammation. 2023 Dec;46(6):2209-2222. (IF-2022 – 5.1)

2. James JV, Varghese J*, John NM, Deschemin JC, Vaulont S, McKie AT, Jacob M. Insulin resistance and adipose tissue inflammation induced by a high-fat diet are attenuated in the absence of hepcidin. J Nutr Biochem. 2022 Oct 9:109175. (IF-2021 – 6.117) * - co-first author

3. Venkatesan P, Ramasamy J, Vanitha S, Jacob M, Varghese J*. Impaired pancreatic beta-cell function after a single dose of oral iron: a before-and-after (pre-post) study. J Hum Nutr Diet. 2022 Aug 24. (IF -2020 - 3.089) – *corresponding author

4. Varghese J*, Jacob M. Gift authorship: Look the gift horse in the mouth. Indian J Med Ethics. 2022 Apr 21;-(-):1-7. – *corresponding author

5. 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  

6. 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

7. 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)

8. 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

9. 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)

10. 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)

11. 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)

12. 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)

13. 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 

14. 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)

15. 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)

16. 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)

17. 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)

18. 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

i. Co-author of Harper’s Illustrated Biochemistry  (32nd edition , 2023) McGraw Hill Lange, USA.

The chapter written is as follows:

• Molly Jacob; Joe Varghese; P. Anthony Weil. Chapter 56: Cancer: An Overview

ii. Co-author of Harper’s Illustrated Biochemistry (31st edition , 2018) McGraw Hill Lange, USA.

The chapters written are as follows:

• Peter J. Kennelly; Robert K. Murray; Molly Jacob; Joe Varghese. Chapter 52: Plasma Proteins & Immunoglobulins

• Molly Jacob; Joe Varghese; P. Anthony Weil. Chapter 56: Cancer: An Overview

iii. Co-author of Harper’s Illustrated Biochemistry (30th edition, 2015) McGraw Hill Lange, USA.

The chapters written are as follows:

• David A. Bender, Joe Varghese, Molly Jacob and Robert K. Murray. Chapter 48. Clinical Biochemistry

• Peter J. Kennelly, Robert K. Murray, Molly Jacob and Joe Varghese. Chapter 52. Plasma Proteins & Immunoglobulins

• Molly Jacob, Joe Varghese, Robert K. Murray and P. Anthony Weil. Chapter 56. Cancer: An Overview

iv. Co-author of Harper’s Illustrated Biochemistry (29th edition, 2012) McGraw-Hill Publishers (Lange)

The chapters written are as follows:

• Robert K. Murray, Molly Jacob and Joe Varghese. Chapter 50. Plasma Proteins & Immunoglobulins

• Robert K. Murray, Molly Jacob and Joe Varghese. Chapter 55. Cancer: An Overview

• Joe Varghese, Molly Jacob and Robert K. Murray. Chapter 56. Clinical Biochemistry

FELLOWSHIPS

1. CDSA Research Training Fellowship (2018) to train at the University of Girona, Spain (Prof. Fernandez-Real’s lab) for a period of 6 weeks.

2. 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.

3. 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. 

AWARDS

1. The Rev. Fr. Lourdu M Yeddanapalli S.J. Award 2021: This award is given to a faculty member in CMC who has made outstanding contributions to research in basic or applied sciences.

2. 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

3. Second prize (oral presentation, faculty members - Basic Science category) at the Annual Research Day in Christian Medical College, Vellore, in 2021

4. Third prize (oral presentation, faculty members - Basic Science category) at the Annual Research Day in Christian Medical College, Vellore, in 2017

5. Drs. Molly and Thomas Bhanu Award for the Best Teacher (2012) - Christian Medical College, Vellore