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Dr. Vinay Bulusu

Assistant Professor

Biological Sciences

vbulusu@iiserbpr.ac.in

6546464654

Personal Website

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Publications All

Academic Background

  • Ph.D from JNCASR, Bengaluru,(2004-10). Graduation (degree): B.Tech in Biotechnology, School of Biotechnology, Guru Gobind Singh Indraprastha University, Delhi. (2000-2004)

Professional Experience 

  • Research Associate at Cancer Research UK Beatson Institute, Glasgow, United Kingdom (2014-19). EMBL Interdisciplinary Post-Doctoral (EIPOD) fellow, EMBL, Heidelberg, Germany (2011-14).

Awards and Memberships

  • Lifetime Member of Society of Biological Chemistry Member of Indian Society of Developmental Biology

Research Interests

  • Metabolic regulation, MS-Metabolomics, Protein based metabolite biosensors

Research Group

  • PhD students: Arabinda Ghosh, Deblina Dhabal, Srijani Saha, Anwesha Manasingh, Chandani Chandrawanshi. Project Assistant: Amrit Patra MS students: Gourav Padhan, Ravikiran

About me

I am a biochemist interested in understanding the metabolic organization and regulation of cellular processes in cancer and embryonic development

Biography

Assistant Professor at IISER Berhampur (from May 2020 – present)

Research Associate at Cancer Research UK Beatson Institute, Glasgow, United Kingdom (2014-19).

EMBL Interdisciplinary Post-Doctoral (EIPOD) fellow, EMBL, Heidelberg, Germany (2011-14).

Ph.D: 
Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, Karnataka, India (2004-10). (2010).
Adenylosuccinate lyase and metabolic fate of fumarate in the intraerythrocytic stages of Plasmodium falciparum.


Graduation (degree): 
B.Tech in Biotechnology, School of Biotechnology, Guru Gobind Singh Indraprastha University, Delhi. (2000-2004)

Research Projects

Research Interests

Our group is interested in understanding the metabolic organization and its regulation of cellular processes like growth, proliferation and differentiation.While the role of thermodynamic and kinetic principles in organizing and driving metabolic reactions are understood, the specific interplay of metabolites and enzymes in modulating signaling and gene transcription is now coming to the fore. During embryonic development and in metabolic diseases such as cancer, cellular fates like cell proliferation and differentiation are associated with specific metabolic states. Using a combination of functional genomics with advanced mass spectrometry, imaging and computational modelling, we aim to understand the metabolic cross-talk with signaling and gene transcription networks in development and disease. The specific questions that we ask are: 


1. How does sub-cellular metabolic compartmentalization help in cancer progression?

In solid tumors, cancer cells face nutrient limitation due to poor vasculature. Under these conditions, cancer cells rewire their metabolism and evolve to acquire alternate nutrients for their growth and proliferation. We and others have previously shown that acetate is one such nutrient that is scavenged by hypoxic and lipid deprived cancer cells (Schug et al., (2015) Cancer Cell. 27(1):57-71., Comerford et al., (2014) Cell159(7):1591-602; Bulusu et al., (2017) Cell Rep.18(3):647-658). Acetate was thought to feed into a common nucleo-cytosolic acetyl-CoA pool to fuel lipid synthesis and histone acetylation. However, our study showed that under hypoxic conditions, nuclear and cytosolic acetyl-CoA pools are compartmentalized by a kinetic barrier enabling exogenous acetate to channel directly into lipid synthesis (Figure 1). We are now pursuing further studies to understand such flux barriers in metabolic compartmentalization and how these help in cancer progression. 

Figure 1: Acetyl-CoA compartmentalization in hypoxic and lipid deprived cancer cells. Adapted from Bulusu et al. Cell Rep.18(3):647-658 (2017)


2. How do dynamic changes in metabolites effect gene expression networks?

Metabolites such as acetyl-CoA and S-adenosyl methionine are important cofactors for DNA and chromatin modifying enzymes. How fluctuations in these metabolites lead to changes in gene expression is being investigated. We are currently developing novel genetically encoded fluorescence-based sensors for such metabolites using protein engineering and modelling approaches with the aim to understand their sub-cellular dynamics. 

3. Role of metabolic gradients incancer and embryonic development?

Altered metabolic activities of the cancer cells and aberrant vascular development leads to development of metabolic and nutrient gradients in solid tumors. In addition to cancer, we and others have previously shown the existence of a glycolytic gradient in mouse embryonic presomitic mesoderm that is essential for anterior-posterior axis elongation and patterning (Bulusu et al., (2017)Dev Cell.40:331-341; Oginuma et al., (2017) Dev Cell. 40: 342-353) (Figure 2). Such gradients have been proposed to confer robustness to nutrient fluctuations. We are currently dissecting the mechanisms of gradient formation and their role using cell culture models in vitroand in future using mouse models in vivo. 

Figure 2: Glycolytic gradient in mouse embryonic presomitic mesoderm. Adapted from Bulusu et al. (2017) Dev Cell. 40: 331-341.

Key Publications

Mahor D, Pandey R, Bulusu V. TCA cycle off, ATF4 on for metabolic homeostasis. Trends Biochem Sci. 2022 Jul;47(7):558-560. 


Michalopoulou E, Auciello FR, Bulusu V, Campbell AD, Karim SA, Morton JP, Sansom OJ, and Kamphorst JJ. Macropinocytosis makes pancreatic tumor cells with PTEN deficiency resistant to mTOR inhibition. (2020) Cell Rep. 30(8):2729-2742


Pucino V*, Certo M*, Bulusu V, Cucchi D, Goldmann K, Pontarini E, Haas R, Smith J, Headland SE, Blighe K, Ruscica M, Humby F, Lewis MJ, Kamphorst JJ, Bombardieri M., Pitzalis C and Mauro C. Lactate build-up at the site of chronic inflammation promotes disease by inducing CD4+ T cell metabolic rewiring. (2019) Cell Metab.30:1055-1074 (*Equal Contribution)


Auciello FR*, Bulusu V*, Chet O, Mulder JT, Berry M, Tumanov S, Allen-Petersen BL, Link J, Kendsersky ND, VringerE ,Schug M, Novo D, Hwang RF, Evans RM, Nixon C, Morton JP, Norman JC, Sears RC, Kamphorst JJ and Sherman MH (2019). A stromal lysolipid-autotaxin signalling axis promotes pancreatic tumour progression. Cancer Discovery 9(5):617-627. (*Equal Contribution).


Bulusu V*, Prior N*, Snaebjornsson MT*, Kuehne A, Sonnen KF, Kress J, Stein F, Schultz C, Sauer U and Aulehla A. (2017) Spatiotemporal Analysis of a Glycolytic Activity Gradient Linked to Mouse Embryo Mesoderm Development. Dev Cell. 40(4):331-341. (*Equal Contribution) 


Bulusu V, Tumanov S, Michalopoulou E, van den Broek NJ, MacKay G, Nixon C, Dhayade S, Schug ZT, VandeVoorde J, Blyth K, Gottlieb E, Vazquez A and Kamphorst JJ. (2017) Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation. Cell Rep.18(3): 647-658.


Contact Details

Full Name

Vinay Bulusu


Email

vbulusu@iiserbpr.ac.in


Contact

6546464654


Address

IISER Berhampur


Personal Website

Not Available