Brant Isakson

Education

  • PhD, University of Wyoming

Primary Appointment

  • Professor, Molecular Physiology and Biological Physics

Contact

Research Interest(s)

Translating our discoveries in the microcirculation to tangible benefits in patients.

Research Description

The etiology of many cardiovascular diseases can be traced to the microcirculation, which is the primary focus of the Isakson lab. For example, high blood pressure as well as strokes or heart attacks are all due to dysfunction at some level in the microcirculation. As the name implies, the microcirculation consists of the smallest arteries and veins, and these small blood vessels are responsible for modulating blood pressure, delivery of oxygen to tissue, and regulating the inflammatory response. The Isakson lab has made important discoveries in each of these areas that includes development of genetically modified mouse models, several patented products, as well as research disclosures. Our research has shown that by altering particular proteins in the blood vessels of the microcirculation, we can drastically lower blood pressure; if we focus on a different set of proteins, we can severely reduce inflammation and damage incurred by stroke or heart attack. We have an ongoing IRB to recruit human volunteers to further test these ideas and pull our research into an eventual treatment modality.

Selected Publications

  • Hong K, Cope E, DeLalio L, Marziano C, Isakson B, Sonkusare S. TRPV4 (Transient Receptor Potential Vanilloid 4) Channel-Dependent Negative Feedback Mechanism Regulates Gq Protein-Coupled Receptor-Induced Vasoconstriction. Arteriosclerosis, thrombosis, and vascular biology. 2018. PMID: 29301784
  • Begandt D, Good M, Keller A, DeLalio L, Rowley C, Isakson B, Figueroa X. Pannexin channel and connexin hemichannel expression in vascular function and inflammation. BMC cell biology. 2017;18 2. PMID: 28124621 | PMCID: PMC5267334
  • Biwer L, Good M, Hong K, Patel R, Agrawal N, Looft-Wilson R, Sonkusare S, Isakson B. Non-Endoplasmic Reticulum-Based Calr (Calreticulin) Can Coordinate Heterocellular Calcium Signaling and Vascular Function. Arteriosclerosis, thrombosis, and vascular biology. 2017;38(1): 120-130. PMID: 29122814 | PMCID: PMC5746467
  • Biwer L, Lechauve C, Vanhoose S, Weiss M, Isakson B. A Cell Culture Model of Resistance Arteries. Journal of visualized experiments : JoVE. 2017;. PMID: 28930992
  • DeLalio L, Isakson B. ZP1609/danegaptide and mitochondrial connexin hemichannels: a harbinger for peptide drug design. British journal of pharmacology. 2017;174(15): 2606-2607. PMID: 28567717 | PMCID: PMC5513857
  • Good M, Chiu Y, Poon I, Medina C, Butcher J, Mendu S, DeLalio L, Lohman A, Leitinger N, Barrett E, Lorenz U, Desai B, Jaffe I, Bayliss D, Isakson B, Ravichandran K. Pannexin 1 Channels as an Unexpected New Target of the Anti-Hypertensive Drug Spironolactone. Circulation research. 2017. PMID: 29237722
  • Keller A, Diederich L, Panknin C, DeLalio L, Drake J, Sherman R, Jackson E, Yan Z, Kelm M, Cortese-Krott M, Isakson B. Possible roles for ATP release from RBCs exclude the cAMP-mediated Panx1 pathway. American journal of physiology. Cell physiology. 2017;313(6): C593-C603. PMID: 28855161
  • Keller A, Isakson B. The Evolving Role of Diverse Gaseous Transmitters Mediating Heterocellular Communication Within the Vasculature. Antioxidants & redox signaling. 2017;26(16): 881-885. PMID: 28288516 | PMCID: PMC5455213
  • Marziano C, Hong K, Cope E, Kotlikoff M, Isakson B, Sonkusare S. Nitric Oxide-Dependent Feedback Loop Regulates Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Cooperativity and Endothelial Function in Small Pulmonary Arteries. Journal of the American Heart Association. 2017;6(12). PMID: 29275372
  • Nyberg M, Piil P, Kiehn O, Maagaard C, Jørgensen T, Egelund J, Isakson B, Nielsen M, Gliemann L, Hellsten Y. Probenecid Inhibits α-Adrenergic Receptor-Mediated Vasoconstriction in the Human Leg Vasculature. Hypertension (Dallas, Tex. : 1979). 2017;71(1): 151-159. PMID: 29084879
  • Liu S, DeLalio L, Isakson B, Wang T. AXL-Mediated Productive Infection of Human Endothelial Cells by Zika Virus. Circulation research. 2016;119(11): 1183-1189. PMID: 27650556 | PMCID: PMC5215127
  • Billaud M, Lohman A, Johnstone S, Biwer L, Mutchler S, Isakson B. Regulation of cellular communication by signaling microdomains in the blood vessel wall. Pharmacological reviews. 2014;66(2): 513-69. PMID: 24671377 | PMCID: PMC3973613
  • Cechova S, Zeng Q, Billaud M, Mutchler S, Rudy C, Straub A, Chi L, Chan F, Hu J, Griffiths R, Howell N, Madsen K, Jensen B, Palmer L, Carey R, Sung S, Malakauskas S, Isakson B, Le T. Loss of collectrin, an angiotensin-converting enzyme 2 homolog, uncouples endothelial nitric oxide synthase and causes hypertension and vascular dysfunction. Circulation. 2013;128(16): 1770-80. PMID: 24048198
  • Lohman A, Billaud M, Isakson B. Mechanisms of ATP release and signalling in the blood vessel wall. Cardiovascular research. 2012;95(3): 269-80. PMID: 22678409 | PMCID: PMC3400358
  • Lohman A, Weaver J, Billaud M, Sandilos J, Griffiths R, Straub A, Penuela S, Leitinger N, Laird D, Bayliss D, Isakson B. S-nitrosylation inhibits pannexin 1 channel function. The Journal of biological chemistry. 2012;287(47): 39602-12. PMID: 23033481 | PMCID: PMC3501028
  • Straub A, Lohman A, Billaud M, Johnstone S, Dwyer S, Lee M, Bortz P, Best A, Columbus L, Gaston B, Isakson B. Endothelial cell expression of haemoglobin α regulates nitric oxide signalling. Nature. 2012;491(7424): 473-7. PMID: 23123858 | PMCID: PMC3531883
  • Billaud M, Lohman A, Straub A, Looft-Wilson R, Johnstone S, Araj C, Best A, Chekeni F, Ravichandran K, Penuela S, Laird D, Isakson B. Pannexin1 regulates α1-adrenergic receptor- mediated vasoconstriction. Circulation research. 2011;109(1): 80-5. PMID: 21546608 | PMCID: PMC3135971
  • Chekeni F, Elliott M, Sandilos J, Walk S, Kinchen J, Lazarowski E, Armstrong A, Penuela S, Laird D, Salvesen G, Isakson B, Bayliss D, Ravichandran K. Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature. 2010;467(7317): 863-7. PMID: 20944749 | PMCID: PMC3006164