Academic Appointments:
Assistant Professor, Chemistry and Biochemistry Department, Brooklyn College, The City University of New York
Faculty, Chemistry, Biology and Biochemistry PhD Programs, The Graduate Center, The City University of New York

Degree(s)
Ph.D. (Chemistry) JNCASR, India
B.Tech. (Biotechnology), SASTRA University, India

Research Focus:
My research program focuses on design and synthesis of controlled ordered domains in liquid biological condensates. The potential applications this encompasses includes their use: a) as a drug delivery vehicle for hydrophobic anti-cancer drugs and b) as a protocell model for chemical signaling. The broad ranging goal of my research is to create drug delivery vehicles capable of programming their actions based on metabolic needs of the cell.

Biomolecular condensates represent a growing area of research, due to their recognized importance in subcellular organization and key role in processes ranging from signal transduction to nucleic acid metabolism. These are membrane-less organelles inside cellular systems working to modulate the metabolic flux by forming localized functional regions which in turn lead to enhanced enzyme activity, selective uptake of reaction components, localized changes in dielectric constants, overall control of binding events, reaction rates and even noise buffering. While condensates represent an exciting therapeutic target due to their high functional relevance, their foray into novel biomaterials is perhaps equally imperative. An exciting area of development is the application of condensates as a drug delivery platform. Higher partition coefficient of bio-relevant molecules inside homogenous phase of condensates indeed makes it a superlative candidate for therapeutics. One could envisage a next generation of platforms that, instead of being a single phase inside, are made up of multiple stable phases that control the spatial distribution of active components inside, allowing the possibility of reaction systems controlling the therapeutic response. Controlled localized structure in a globally liquid droplet would not only enhances the partition coefficients of prospective drug molecules (For example hydrophobic anti-cancer drug molecules such as Tivantinib, Crizotinib, and Palbociclib) but will also be capable of stimuli sensitive, reversible, and multifarious action. Even though biomolecular condensates are globally disordered, they perform efficient biological functions through ordered domains present inside them. Understanding and ultimately controlling the local architecture of these liquid droplets is thus imperative if one were to gain deeper functional insights into their means of operation and apply them in diverse fields. Recently, we designed a multi-component system such that the interface between ordered and disordered domains is stabilized through a covalent connection of beta sheet-promoting and condensate-forming features. This allows beta sheet fibers to form exclusively inside the droplets and show clear fiber nucleation and elongation stages. This study shows for the first time that minimalistic ordered domains can be generated inside liquid droplets in a controlled fashion and my research leverages these design principles to develop systems for programmable therapeutics.

Selected Publications:

A. Jain, S. Kassem, R. S. Fisher, B. Wang, T.-D. Li, T. Wang, Y. He, S. Elbaum-Garfinkle, and R. V. Ulijn, Connected peptide modules enable controlled co-existence of self-assembled fibers inside liquid condensates, J. Am. Chem. Soc. 144, 15002-15007 (2022). Equal contribution first author and co-corresponding author. https://pubs.acs.org/doi/10.1021/jacs.2c05897

A. Jain, S. A. McPhee, T. Wang, M. N. Nair, D. Kroiss, T. Z. Jia and R. V. Ulijn, Tractable molecular adaptation patterns in a designed complex peptide system, Chem, 8, 1894-1905, (2022). https://www.sciencedirect.com/science/article/pii/S245192942200153X

A. Jain, S. Dhiman, A. Dhayani, P. K. Vemula and S. J. George, Chemical fuel-driven living and transient supramolecular polymerization, Nat. Commun. (2019). https://www.nature.com/articles/s41467-019-08308-9

A. Jain, A. Achari, N. Mothi, M. Eswaramoorthy and S. J. George, Shining the Light on Clay-Chromophore Hybrids: Layered Templates for Accelerated Ring Closure Photo-Oxidation, Chemical Science, 6, 6334-6340 (2015). https://pubs.rsc.org/en/content/articlelanding/2015/sc/c5sc02215k

F. Sheehan, D. Semanta, A. Jain, M. Kumar, M. Tayarani, D. Kroiss and R. V. Ulijn, Peptide-based supramolecular systems chemistry, Chem. Rev. 121, 13869-13914, (2021). Equal contribution first author. https://pubs.acs.org/doi/10.1021/acs.chemrev.1c00089