Cellular and Molecular Biology Faculty Research Interests

RNA viruses present a threat to both human and animal health and can have severe public health and economic consequences. Once a virus enters the cell it must rapidly amplify its genome and avoid host defense mechanisms. Viral replication is a highly regulated process that involves the interaction between viral proteins and host proteins to manipulate different cellular pathways for virus survival. At the same time, the infected organism activates an immune response to the virus to counteract the infection. The competition between the virus and the host immune response ultimately determines the outcomes of the infection. Therefore, understanding how the virus replicates in the host and avoids the immune system is critical for the design of antiviral strategies and vaccine development.

Our laboratory combines molecular biology, virology and biochemistry approaches to investigate viral replication in cells. We use molecular biology techniques to design replicons – genetically altered viral genomes – to identify determinants important for viral genome synthesis. Furthermore, we utilize yeast, Saccharomyces cerevisiae, to identify novel host proteins that may influence viral replication. We are very interested in the in-depth characterization of potential viral proteins that interact with host proteins to determine how we can better develop vaccines or new antiviral strategies to control viral infection.

The Lyme disease research group investigates the different forms of Borrelia burgdorferi, the causative agents of Lyme disease, to better understand how Borrelia can hide from the immune system as well as from antimicrobial therapies. Our recent research shows that Borrelia burgdorferi is capable forming a protective layer around itself – called biofilm – which could render it to be very resistant to antibiotics and provide a logical explanation as to why extensive antibiotic treatment for patients with a tick-bite history could fail. The goal of our research group is to fully characterize this novel form and to identify novel antibacterial agents that are effective in killing all forms of Borrelia burgdorferi

DNA Damage, DNA Repair and Neurodegeneration: We study how induced level of oxidative stress and/or impaired DNA repair can contribute to pathogenesis of neurodegenerative diseases. Poor DNA repair system and exposure to high levels of free radicals such as reactive oxygen species can demolish neural cells and potentially lead to neurodegeneration. This can be a crucial factor in neurodegenerative diseases, as neurons seem to be among the most sensitive cells.

Lyme disease, Inflammation and Neurodegeneration: In collaboration with Dr. Sapi’s group we study if Lyme disease causing bacteria, i.e. Borrelia burgdorferi, in addition to causing potential chronic inflammatory conditions, may also cause or contribute to the development of neurodegeneration. To do so we evaluate both the types and the consequences of DNA damage, occurring in cells and tissues of animal (i.e. zebrafish) and patients exposed to the bacteria or microvesicles.

DNA damage and Cancer: We are interested to study how harmful environments and high level of free radicals can cause DNA damage leading to cancer. We would like to evaluate the level of DNA damage in both normal and cell that are lacking key DNA repair genes such as BRCA, which is found in some breast cancer patients treated with radiation and several compounds. This should help us understand a potential mechanism of how people who are carrier of defected DNA repair gene such as BRCA can become more susceptible to cancer; especially breast and ovarian cancer.”

Antioxidants: Which one and how much of them is good. We study how the level and impact of reactive oxygen species can be neutralized by antioxidant such as Green tea, Saffron, NAC, polyphenol resveratrol. This would help us identify the right antioxidant and dose that can for instance help patients who receive radiation or being treated with drugs such as Menadione.

My research program has two branches that are related through studying microbial communities and interactions: 1) profiling microbial communities and succession of these communities in unique ecological niches, and 2) examining cultured bacterial isolates from these communities and how interactions between distinct community members elicit the production of unique colony phenotypes (sporulation, motility) or small molecules (antibiotics or anti-biofilm agents). My research employs various techniques including basic microbiology techniques, sequencing and genomic analysis, molecular biology and cloning, and analytical techniques. My research questions can help answer outstanding questions in microbial ecology, and may lead to the discovery of novel and clinically relevant anti-microbial compounds.

We all begin our journey in life as single fertilized cells that divide into millions of progeny cells. Our transformation into complex bodies involves dynamic and coordinated changes in which genes are ‘expressed’ in each cell or, more specifically, which RNAs are produced from those genes. These RNAs serve as instructions that guide cell organization and movement, as well as direct different cells to become particular cell types (e.g. brain, skin). My research interests lie in understanding the mechanisms, and downstream functions, of RNA regulation during embryo formation. How are previous RNAs removed to enable new developmental gene programs? What factors in the embryo dictate how long an RNA persists? What sequence features of an RNA impact its stability in the cell? Finally, how does the production and/or removal of different RNAs shape cellular movements, tissue formation, and cell identity? To answer these questions, my lab utilizes the zebrafish model system to study the role of RNA regulation within the context of early development and brain morphogenesis.

Why zebrafish? Zebrafish are becoming a very popular model organism to study almost every aspect of cell and developmental biology. Zebrafish can generate hundreds of embryos in a single morning that are easy to collect and study. The embryos develop rapidly and are transparent, allowing for real-time imaging of cellular processes. In addition, the genome is sequenced, and many genetic tools, such as CRISPR-based genome editing, work exceptionally well in this model organism. In my lab, we couple these tools with biochemical techniques and microscopy to understand how gene regulation shapes biological form. Ultimately, we hope that the insights gained from this work will inform our understanding of human biology and disease.

My overall interest is in the role of protein kinases and protein phosphatases in oncogenesis. An understanding of how these proteins function not only gives us more information about how cancer develops, but these kinases and phosphatases also can be targets for anti-cancer therapy. We use many of the cell culture and molecular biology techniques that are taught in the labs at the University of New Haven to study the signaling pathways that regulate cancer cell growth and invasion. Currently there are two areas of focus in my lab:

1. Crosstalk between skeletal muscle and breast cancer cell lines

   • There seems to be a harmful recipricocal relationship between cancer cells and skeletal muscle. Patients with cancer often suffer from cancer induced muscle wasting. This calchexia is caused by both a depletion of nutrients and by cross talk between the cancer cell and the muscle cell. Conversely, muscle cells which may be proliferating or differentiating secrete factors that affect cancer cell growth and invasion. One of our research goals is to investigate the signaling pathways that are activated during these cancer/ muscle cell crosstalk.

2. Growth and invasion of non-HPV related cervical cancer

   • Most cases of cervical cancer are related to infection with the Human Papilloma Virus. However, a small number of cervical cancers are not associated with HPV infection, and I am interested in studying the signaling pathways that are activated in these cervical cancer patients.