Faculty Research Interests
Human cytomegalovirus pathogenesis and persistence.
Understanding the epidemiology and pathogenesis of viral hemorrhagic and encephalitic arboviruses and host-vector interactions.
My research is primarily focused on defining the role of SHIP1 in immunity, obesity, stem cell biology and cancer. This research has revealed that SHIP1 is at the nexus of signaling pathways that regulate: (1) hematopoietic and mesenchymal stem cell homeostasis, (2) terminal differentiation of myeloid cells, (3) acute BM graft rejection, (4) survival of T cells in the small intestine and (5) survival of hematologic cancer cells. More recently we developed SHIP1 and pan-SHIP1/2 inhibitors and showed they can expand stem cells in vivo, reverse obesity, eradicate certain cancers and boost tumor immunity. We are also attempting to better understand what LRBA does in immune cells. LRBA is a scaffold protein that coordinates intracellular vesicle trafficking with receptor signaling.
My group is interested to identify functional consequences of defect membrane anchor synthesis in innate immune cells. We study particularly the effect on membrane-bound versus soluble molecules that derive from monocytes. A dysregulation of the membrane-to-soluble ratio could have a direct impact on the development of conditions such as atherosclerosis through skewed macrophage differentiation and metabolic reprogramming, lipid uptake and foam cell formation. Further, the generation of excessive amounts of damaging reactive oxygen species may lead to metabolic exhaustion in these cells in response to infections. We are also investigating the mechanistic basics of mitochondrial dysfunction and innate immunity activation as a driver of systemic inflammation and comorbidity risk factors in obesity.
My laboratory is interested how the activation and potential dysregulation of the innate immune system contributes to the onset and progression of autoimmune diseases such as Systemic Lupus Erythematosus (SLE). We were initially researching if and how viral RNAs can trigger SLE-like symptoms, and interestingly we found intracellular, antiviral pathways that converge at mitochondria can be activated in SLE patients in the absence of any viral infection. This activation correlates with the high type I interferon (IFN) signature which is characteristic for individuals with SLE. We found that oxidative stress plays an important role in the dysregulation of these innate immune pathways. Therefore, we have expanded our research to identify environmental factors that generate oxidative stress, which in turn leads to metabolic dysregulation and ultimately to SLE pathology. Our long-term goal is to develop refined approaches to diagnose the causes of SLE, and to stratify therapeutic treatments for SLE patients.
Varicella zoster pathogenesis.
Host antiviral responses and Herpesviruses
Translational medicine with a focus on novel therapeutics and vaccines; Lyme and tick borne diseases.
Genes and Viruses Predisposing to Autoimmunity, Genetics, Apoptosis, Endogenous Retroviruses, Transaldolase
Investigate the role of Cx43 gap junctions and hemichannels in immunity
My laboratory seeks to advance our understanding of the interplay between the host immune response and metabolic status in the context of both acute and chronic viral infections (e.g., HIV-1 and SARS-CoV-2). Our efforts are aimed at informing strategies with the ultimate goal of reducing the burden of these viral infections in high-risk populations.
- Effect of co-infection on the clinical outcome of Lyme disease and Powassan encephalitis.
- Impact of ecological changes on geographic expansion of Powassan virus and other tick borne diseases in Upstate New York.
- Tick and tick borne diseases surveillance in Upstate New York.
- Tick determinants of Powassan virus transmission.
- Arthropod-virus-host interface: Nidus of arbovirus transmission.
- The effect of mosquito salivary factors on Chikungunya and Zika virus infection and dissemination.
- Development of tick transmission model for Heartland virus pathogenesis.
- Ecology of Infectious Diseases
Virology, Countermeasure Development, Global Health Security.
My group is dedicated to understanding how the interactions between infectious organisms and the human immune system result in pathogenesis and/or durable immunity. Our work is primarily focused on viral pathogens, and leverages \"next generation\" technologies such as single cell RNA sequencing, multi-parametric flow cytometry, and computational modeling.
Understanding plasma cell and antibody longevity with a focus on host-microbiome interactions and IgA responses that lead to protection during sepsis.
Research Professor Emeritus
Host defense against intracellular pathogens, B cell responses, immunological memory