Page 39 - Annual report 2021-22

Annual Report 2021-22 |

Shantanu Sengupta

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Shantanu Sengupta’s lab employs proteomics and metabolomics tools to understand metabolic
diseases. Shantanu’s lab has been studying one carbon metabolism with interest in its role in
cardiovascular diseases.

Vitamin B12 is an essential cofactor required in one carbon metabolism and low levels of Vitamin B12
are associated with high risk of cardiovascular disease. His lab uses the rat model to understand the
transgenerational impact of paternal and maternal Vitamin B12 deficiency. Using label-free
quantitative proteomics, his group analyzed the proteomic change in the liver of offspring born to
vitamin B12 deficient fathers with respect to controls. They analyzed liver tissue in F1&F2 generations
at 3 months and 12 months; they identified and quantified 2245 proteins across all samples, out of
which the expression of 164 and 56 proteins were altered in males and females respectively at 3
months in F1 generation. Altered protein levels were more distinct in male liver in F1 12 months where
the expression of 490 proteins and 159 were altered in males and females respectively. There was
little overlap of altered proteins in males and females, indicating a gender specific proteome
reprogramming in the liver due to paternal vitamin B12 deficiency. In a collaborative study, Shantanu’s
lab is also involved in estimating the prevalence of Vitamin B12 deficiency in India. One of the major
objectives of the project was to estimate the vitamin B12 deficiency and the results revealed that the
deficiency across ages is about 15 to 20%. However, deficiency of active B12 (holoTC) was considerably
higher. In adolescent males and females, the deficiency of active B12 was around 40%. Active B12 is
the B12 that actually enters into the cells. As a consequence of deficiency of holoTC, the levels of
homocysteine were higher in 45 to 50% adolescent males and females. This suggested that
determining the values of holoTC may be more appropriate than measuring total vitamin B12 levels.
Statewise, it was found that Gujarat had the highest deficiency in vitamin B12 while Assam had the
lowest burden of vitamin B12 deficiency.

The approach of label-free quantitative proteomics is being undertaken in Shantanu’s lab to address
several unmet clinical needs. His lab has also been involved in proteomic analysis of celiac disease in
a multicentric cohort, a project led by AIIMS. In this study, label-free quantitative proteomics was
undertaken towards identification of a biomarker for Celiac disease. The study has identified 12
potential biomarkers which will be further validated in a larger number of samples. Proteins that
distinguish Celiac disease from controls and other enteropathies will be selected for potential
deployment in clinical settings. Similarly, he is collaborating with the Cardiology department at AIIMS
where the goal is to discover a novel prognostic biomarker in patients with acute heart failure.
Following up on the initial discoveries, an MRM panel for 15 protein markers has been created which
needs to be validated in heart failure samples. In a collaboration with IIT Mandi, similar approaches
are being used to identify biomarkers of dilated cardiomyopathy.

Cardiovascular disease surfaced as one of the major risk factors for severe COVID19 disease. In
collaboration with Government Institute of Medical Sciences Noida, Shantanu undertook a proteomic
and lipidomic investigation on blood samples from across three time points for COVID patients across
a spectrum of disease severity. Proteins like albumin, ceruloplasmin, Apo A1, haptoglobin, alpha-1-