Research Journey

In 2012 AIIMS convocation, with Mr. Ghulam Nabi Azad  (Indian Education Minister at the time).

Image Credit : http://mpcrafts.com/product/madhubani-painting-king-queen-perform-worship-big/

"I have no special talent. I am only passionately curious."

-Albert Einstein

My long-term goal as a scientist is to gain the molecular insights into cell signaling and epigenetic pathways that will be helpful to develop potential drug targets against cancer development and relapse. My research motto is “Target the untreatable roots of cancer”.

I was born in Madhubani district of Bihar state in India. My birth place is widely popular for classical art named Mithila Painting or Madhubani painting. I did my schooling and advanced studies from New Delhi, India.

 

My journey towards cancer biology and hematological malignancy research started in 2010 when I joined master’s program (M.Sc. in Biochemistry) at All India Institute of Medical Sciences (AIIMS) New Delhi, a premier medical institute in India. Every year only 4 students are selected from throughout India to pursue this course, based on a written entrance examination and overall previous academic performance. Over the years, I have recognized my passionate interest towards academic research and a strong analytical aptitude, perseverance and resilience for problem solving that has led me to pursue a career in research. My undergraduate courses and graduate research have provided me with a sound academic foundation in cancer biology, stem cell biology, biochemistry, immunology, and molecular biology. During these trainings, I have also acquired other essential skillsets which are instrumental to become an independent researcher such as the ability to critique primary research, write research grants, analyze data, problem-solving, collaborations and develop novel ideas. A lot of my interpersonal skills also come from being the first woman, the first-generation PhD graduate and the first-generation immigrant altogether in my entire family and community.

 

From the beginning of my studies, I have been closely associated with clinical and molecular research, accredited to my master’s thesis project with Dr. Alpana Sharma in the Department of Biochemistry at All India Institute of Medical Sciences, New Delhi. During my time in the lab, I worked closely with multiple myeloma and leukemia patients in Dr. Sharma’s lab, which inspired me to study cancer at its core. Under her guidance, I studied one of the most prominent molecular players in cancer initiation and development, Wnt/b-catenin signaling. To execute my project on myeloma cell lines, I had personally setup the cell culture facility in the lab, which lab is still utilizing to answer patient relevant questions.  Wnt/b-catenin signaling is upregulated in multiple myeloma (MM) and therapeutically difficult to target in myeloma patients. This signaling is also responsible for drug resistance and relapse in several multiple myeloma patients. Specifically, two downstream transcriptional targets of Wnt/b-catenin signaling, VEGFA and c-Myc are significantly correlated with poor prognosis and reduced survival in MM. In my study, I demonstrated the therapeutic efficacy and molecular mechanism of a pharmacological agent isolated from a soil amoeba Dityostelium discoideum, Differentiation Inducing Factor-1(DIF-1) on MM cells growth and proliferation. Utilizing molecular biology techniques such as qPCR and western blotting, I found that DIF-1 decreases the levels of VEGFA and c-Myc at both RNA and protein levels. This study led to a first-authored publication in International Journal of Hematology and Oncology (Kumari R et al, 2016). After this study, DIF-1 has been explored in several other cancers, such as triple-negative breast cancer, colon cancer and glioblastoma for its therapeutic efficacy (Ito R et al, 2020; Seto-Tetsuo F et al, 2021).

 

To advance my scientific knowledge of cancer development and to attain my graduate degree, I moved to Dr. Sanjeev Das’s lab to pursue PhD in molecular oncology at one of the most prominent research institutes in India, the National Institute of Immunology (NII), New Delhi. Dr. Das himself has been trained in molecular oncology at the premier cancer research institute, Massachusetts General Hospital and Harvard Medical School, US and have published groundbreaking molecular findings in journals like Cell, Molecular cell, PNAS and several others. His lab at NII primarily focuses on studying the molecular pathways involved in p53-mediated tumor suppression. p53 is a tumor suppressor gene and guardian of the genome. Its relevance in cancer research is highlighted by the findings that established approximately 50% of the cancers worldwide carries mutation in p53 gene. During my time in the lab, I also focused on studying molecular regulation and functions of p53, one of which was to study the histone deacetylase HDAC5-mediated temporal regulation of p53 transactivation upon genotoxic stress. This study demonstrated how selection of p53 downstream transcriptional targets is dependent on its post-translation modification (acetylation/deacetylation of Lys120 in p53 protein) upon genotoxic and oxidative stress in the cell. This study was published in Molecular Cell as the one of the featured articles. 


For my PhD thesis, I took up one of the most challenging projects in the lab at that time which several other students and postdocs had failed to demonstrate previously. I studied the unknown and unexpected non-canonical function of a caspase and a p53 target, caspase-10. Using adenovirus-mediated overexpression system and proteomics screening, we demonstrated that caspase-10 cleaves metabolic enzyme ATP-citrate lyase (ACLY) under metabolic stress. ACLY is one of the central players in cancer metabolism. Cleavage of ACLY by caspase-10 further altered the metabolic and epigenetic state of cancer cells, which demonstrated the yet unknown tumor suppressive functions of caspase-10, apart from its traditional role in apoptosis. This study was published in Nature Communications in 2019. My research on caspase-10 has not only led to more understanding of caspase-10 in cancer but has only contributed to the understanding of T-cell mediated immunity, cancer immunotherapy, obesity, and several other autoimmune pathologies (based on the citing publications). Moreover, I published two review articles in Molecular and Cellular Oncology, and Current Science which enhanced my understanding of key oncogenic pathways and has been crucial as a literature review for several other research groups trying to understand the role of p53 in development, cancer, and immunity. My study on p53, caspase-10, and ACLY has been nationally and internationally recognized and I have been honored with prestigious awards such as Indian National Science Academy medal for Young Scientist in 2020 and several travels support awards from Government of India (Department of Science and Technology, Department of Biotechnology), Oncotarget Journal, and Talwar Foundation India to present my work internationally in USA and Singapore.

 

To furnish my career in scientific research and follow my interests in basic and translational leukemia research, I joined Dr. Ulrich Steidl’s lab at Albert Einstein College of Medicine in June 2018. Dr Steidl is a world leader in leukemia research with a proven publication and grant track record at the Albert Einstein College of Medicine, New York. His lab has established rigorous experimental systems, cutting-edge methodologies, and both human and mice models for studying the molecular (genetic and non-genetic), cellular and physiological biology of normal hematopoiesis and leukemia. The molecular understanding and pharmacological targeting of aberrant transcription involved in leukemic stem cells at the stage of pre-leukemia or maintenance during relapse is a rapidly emerging field of investigation and Dr. Steidl and collaborators have been proponents and pioneers of these approaches. With the aid and training from the expert research team in Dr Steidl’s laboratory, I have gained several technical and analytical expertise such as cutting-edge single-molecule mRNA FISH technique and closely working with clinically relevant leukemia mice models to decipher therapeutically targetable early molecular events in leukemia development. One of these projects is independently funded by prestigious philanthropic Leukemia and Lymphoma Society. The aim of the project to find the role of a non-classical homeodomain protein, HLX, in leukemia development and progression. HLX is found to be significantly overexpressed in more than 80% Acute Myeloid Leukemia patients, and I believe exploring its function at molecular level will be beneficial for various molecular subtypes of AML. AML is a clonally complex disease and even though classical chemotherapy has been around from last 50 years, we still lack significant treatment remedies to treat leukemia from its roots and abolish the relapse of this cancer. Clinical and molecular investigations have suggested the role of hidden and quiescent (non-dividing) pre-leukemic stem cells in the emergence of relapsed AML cases. In this attempt to understand these pre-leukemic stem cells and early leukemia development events, I am also doing another major project in lab where I am studying single molecule and single cell transformations events in pre-leukemic stem cells. Conclusion of both these projects will shed light on major steps of leukemia evolution, pre- and post-relapse of this disease.

 

Along with these projects, I have been part of several other ongoing projects in the lab which led to publications in journals like Nature Immunology, Blood, Cancer Cell, and Experimental Hematology. 

 

My future goal is to establish my own research group where I can advance basic and translational aspects of cancer evolution, influenced by cell-intrinsic (transcription, genetic and non-genetic events) and cell-extrinsic (aging, metabolism, and microenvironment) factors. As a researcher, this will be my greatest contribution to the humanity worldwide.