Intercellular communication is required for appropriate coordination of cellular metabolism and signal transduction. A unique family of membrane proteins, called connexin and pannexin channels, are critical for properly integrating signals between cells in every organ of the body. To date, 21 connexin and 3 pannexin genes have been identified in the human genome. Importantly, human connexin gene mutations are directly linked to a variety of diseases, including deafness, blindness, skin and neurological disorders. Furthermore, non-inherited diseases, such as cardiac ischemia, brain trauma and epilepsy also alter connexin and pannexin expression and function, resulting in inflammation, tissue dysfunction and cell death. The long-term goal of our research program is to define molecular and cellular determinants that regulate connexin and pannexin function in physiological and pathophysiological contexts. To accomplish this goal, our laboratory uses a variety of techniques including molecular biology, biochemistry, electrophysiology, and behavior. Moreover, a major goal of my lab is to develop novel techniques to quantitatively evaluate connexin and pannexin channel activity. Currently, we have two major lines of funded research for: 1) Determining the contribution of pannexin channels to neuroinflammation and 2) investigating regulation of connexin hemichannels in cardiac stress and arrhythmias.
Funding:
Active
2022–2026 R01 GM099490-11
Title: Gating and regulation of connexin hemichannels
Role: Principal Investigator
Agency: National Institute of General Medical Sciences
2018–2023 R01 HL141170-04 (MPI)
Title: Connexin43: a new player in Duchenne muscular dystrophy associated cardiomyopathy
Role: Principal Investigator (Multi-PI with Diego Fraidenraich)
Agency: National Heart, Lung and Blood Institute
2022–2024 R21 HL163930-01
Title: Role of S-nitrosylated Cx43 in normal cardiac contractility
Role: Principal Investigator
Agency: National Heart, Lung and Blood Institute
Completed
2019–2022 Individual Research Grant, NJCBIR
Title: Role of Microglia/Monocyte Pannexin-1 in Blood-Brain Barrier Disruption and Leukocyte Infiltration after Traumatic Brain Injury
Role: Principal Investigator
Agency: New Jersey Commision for Brain Injury Research
2018–2020 Fellowship AHA (Lillo, PI)
Title: S-nitrosylation of connexin 43 underlies cardiac arrhythmias in muscular dystrophy
Role: Sponsor
Agency: American Heart Association
2015–2018 Individual Research Grant, NJCBIR
Title: Pannexin hemichannels as a therapeutic target for traumatic brain injury
Role: Principal Investigator
Agency: New Jersey Commision for Brain Injury Research
2011–2016 R01 GM099490-05
Title: Gating and regulation of connexin hemichannels
Role: Principal Investigator
Agency: National Institute of General Medical Sciences
2013–2017 R01 GM101950-04 (MPI)
Title: Regulation of Cx26 and Cx32 Channels by Cytosolic Interdomain Interactions
Role: Principal Investigator (Multi-PI with Andrew Harris)
Agency: National Institute of General Medical Sciences
20011–2012 Seed Grant
Title: Regulation of the connexin channel that produces deafness and skin disorders
Role: Principal Investigator
Agency: UMDNJ Foundation
2012–2013 Seed Grant
Title: Molecular basis and modulation of cardiac intercellular communication
Role: Principal Investigator
Agency: UMDNJ Foundation
2014–2016 Fellowship NJCBIR (Garg, PI)
Title: Pannexin hemichannels as regulators of inflammation after traumatic brain injury
Role: Sponsor
Agency: New Jersey Commision for Brain Injury Research