Dr. Rama Kamesh Bikkavilli’s cancer biology training began with his Doctoral research at the Chinese University of Hong Kong, Hong Kong. After completion of his graduate research, he moved to Stony Brook University, New York, for his post-doctoral training in the laboratory of Dr. Craig Malbon. After a brief stay at the University of Colorado, Denver, Dr. Bikkavilli accompanied his mentor, Dr. Robert A. Winn to the University of Illinois at Chicago and joined the team as an Assistant Professor in the Department of Pulmonary, Critical Care, Sleep and Allergy.
Lung cancer cells gain survival and proliferative advantage over normal lung cells by a multitude of molecular mechanisms. One such mechanism is silencing of control of cell division. Recently it was proposed that cancer cells have increased methylation of the amino acid arginine as a means of enhancing cancer cell proliferation.
Dr. Bikkavilli’s research aims at identifying a new class of targets for lung cancer treatment. Dr. Bikkavilli will be working on a class of enzymes called protein arginine methyl transferases (PRMTs) that are poorly studied in lung cancer. Recent work from Dr. Bikkavilli and other researchers around the world identified that these enzymes are upregulated in Cancers. Dr. Bikkavilli will explore the role of PRMT-mediated methylation on ILF2/ILF3 complex formation and the subsequent down regulation of p53, a tumor suppressor protein. He will also test the utility of arginine methylation patterns on proteins as “barcodes” for early detection and screening of lung cancer.
Dr. Bikkavilli’s work focuses on understanding this newly discovered mechanism of malignant behavior by cancer cells. He proposes developing a biomarker assay to detect very early stages of lung cancer by testing for the presence of arginine methylation on ILF2/ILF3. Early detection would allow earlier surgical removal of lung tumors, thus improving prospects for a cure. A further goal is to develop novel lung cancer therapy targeting the process of arginine methylation of ILF2/ILF3 transcription factors.
Final Report: Dr. Kamash Bikkavilli
September 2016 – We would like to share with ABOHLF the summary of research performed during the period of ABOHLF research fellowship award (2014-2016). We were successful in completing Aim 1 by identifying the mechanism of Interleukin Enhancer Binding Factor 2 (ILF2)-mediated lung tumorigenesis. ILF2 is a component of nuclear factor of activated T-cells (NFAT) transcription factor, which is required for T-cell expression of cytokines.
We have identified a novel role for ILF2 in the regulation of a pro-inflammatory cytokine that has been implicated in the pathogenesis of lung cancer via the induction of chemotaxis and macrophage infiltration. We believe that increased expression of ILF2-mediated pro-inflammatory cytokine would contribute to a microenvironment favoring tumor growth via enhanced proliferation and angiogenesis.
All the data generated during the funding period were included in the manuscript for publication in an international, peer-reviewed, high-impact journal. We also affirm that the funding from ABOHLF will be acknowledged in the manuscript. We are happy with our progress, and are excited to submit a grant application to the National Institutes of Health (NIH) for the continuation of our studies.
All these accomplishments would not have been possible without the support of ABOHLF. Thank you.
Progress Reports: Dr. Kamash Bikkavilli
August 2015 – We are excited to share our research progress for the ABOHLF research fellowship award. The major progress made during the last six months of the research program is the identification of a pro-inflammatory cytokine as an important downstream target of ILF2. The identified cytokine has been implicated in the pathogenesis of lung cancer via the induction of other pro-inflammatory mediators like that of TNFa, chemotaxis, and most importantly macrophage infiltration.
Of note, these conditions would greatly contribute to a microenvironment favoring tumor growth via enhanced cell proliferation and angiogenesis. Cancer immunology is a growing field of research, which aims at identifying new ways to utilize the patient’s immune system to fight cancer. Our research findings indicate that the identified cytokine is responsible for cancer-related inflammation. Therefore targeting PRMT6/ILF2-mediated cytokine expression might represent a novel strategy to boost patient’s immune system to fight lung cancer.
November 2014 – We are glad to share with ABOH that clear progress is being made in our research program for the ABOH research fellowship award.
The major progress made during the first six months of the research program was the identification of specific arginines residues on ILF2 as target residues for protein arginine methyl transferases (PRMT1) methylation. We are very excited since these findings would allow us to focus our attention on these mutants to decipher the function of ILF2 in lung tumorigenesis. We also plan on developing specific antibodies, which can be tested as potential lung cancer specific biomarkers.