Joseph Jude, B.V.Sc., Ph.D.
Assistant Research Professor, Department of Pharmacology & Toxicology, Ernest Mario School of Pharmacy
Assistant Professor, Department of Pharmacology, Robert Wood Johnson Medical School
Rutgers Institute for Translational Medicine and Science
Child Health Institute of New Jersey
Rutgers, The State University of New Jersey
89 French Street
New Brunswick, NJ 08901
Fax: (732) 235-7178
Ph.D., University of Minnesota, St. Paul, MN
B.V.Sc., University of Peradeniya, Sri Lanka
University of Pennsylvania, Philadelphia, PA
University of Minnesota, St Paul, MN
Airway smooth muscle (ASM) cells contribute to asthma pathology through their synthetic and mechanical (contractile) functions. Dr. Jude is interested in the molecular and cellular signaling mechanisms of ASM cells in airway disorders such as asthma. His current research focus is on the mechanisms of airway hypersensitivity exacerbation by environmental pollutants like ozone. Ozone and other environmental pollutants are associated exacerbation of clinical signs in asthmatic patients.
- Obesity alters airway smooth muscle phenotype
Obesity is associated with both allergic and non-allergic asthma. Our recent findings show that airway smooth muscle cells isolated from obese human donors have are hyper-reactive to contractile agonists. We have done a phospho-proteomics/proteomics screening to understand the proteomic signature of obese-donor derived ASM cells. Newer protein targets are being pursued to determine how obesity is linked to enhanced ASM cells shortening.
- Sensitizers act on airway smooth muscle and epithelial cells to modulate alarmin secretions and functions
Allergic and non-allergic asthma are exacerbated by environmental toxicants. Many of these toxicants are either occupational or ambient by origin. Our studies showed that exposure to ambient toxicant (formaldehyde in tobacco smoke) or occupational toxicant (DNCB) alter ASM cell function. Alarmins are a group of mediators secreted generally by airway structural cells in response to toxicant/pathogen exposure. Current experiments focus on how alarmins induced by specific toxicants (i.e: DNCB) regulate excitation-contraction coupling in ASM cells. We also focus on how these alarmins render the ASM cells insensitive to bronchodilators, a critical part of asthma therapy.
- Free fatty acid receptors regulate excitation-contraction coupling in airway smooth muscle cells
Free fatty acid levels are elevated in obese subjects. Receptors for some of these free fatty acids are expressed and functional in ASM cells. We are testing a hypothesis that free fatty acid receptors (FFAR) modulate excitation-contraction coupling in ASM cells.
- Cyclic AMP (cAMP) pump expression and function in airway smooth muscle cells
Cyclic AMP (cAMP) is an intracellular second messenger. It is elevated upon activation of beta2 adrenergic receptor (b2AR) on ASM cells. Bronchodilators, such as albuterol, act on b2AR to relax ASM. Recent reports showed that a cAMP pump, called ABCC1/4 (MRP1/4) is expressed in ASM cells. Pumping of cAMP by these proteins may reduce intra-cellular cAMP, therefore attenuate b2AR-induced ASM relaxation. Current experiments focus on expression levels of these proteins in ASM cells in non-asthma and asthma human donors.
- ANO1/TMEM16A: A chloride channel with potential role in cellular Ca2+ dynamics in airway smooth muscle cells
Membrane depolarization is one way of regulating voltage-sensitive Ca2+ channels in excitable cells, such as smooth muscle cells. Anoctamin 1 (ANO1) is a Ca2+-activated-Chloride channel expressed in ASM cells. Studies showed that inhibiting ANO1 with drugs, such as benzbromarone, attenuates contraction in human small airways. The current studies focus on regulation of ANO1 expression by various cytokines and the functional effects in ASM cells as the result of modified expression.
- Obesity increases airway smooth muscle responses to contractile agonists. Orfanos S, Jude J, Deeney BT, Cao G, Rastogi D, van Zee M, Pushkarsky I, Munoz HE, Damoiseaux R, Di Carlo D, Panettieri R Jr. Am J Physiol Lung Cell Mol Physiol. 2018. 315(5):L673L681.
- Salicylic acid amplifies Carbachol-induced bronchoconstriction in human precision-cut lung slices. Jude J, Botelho D, Karmacharya N, Cao GY, Jester W, Panettieri RA Jr. Respir Res. 2019 Apr 11;20(1):72.
- Novel identification of the free fatty acid receptor FFAR1 that promotes contraction in airway smooth muscle. Mizuta K, Zhang Y, Mizuta F, Hoshijima H, Shiga T, Masaki E, Emala CW Sr. Am J Physiol Lung Cell Mol Physiol. 2015 Nov 1;309(9):L970-82.
- A role for multidrug resistance protein 4 (MRP4; ABCC4) in human dendritic cell migration. van de Ven R, Scheffer GL, Reurs AW, Lindenberg JJ, Oerlemans R, Jansen G, Gillet JP, Glasgow JN, Pereboev A, Curiel DT, Scheper RJ, de Gruijl TD. Blood. 2008 Sep 15;112(6):2353-9.
- Activation of Ca(2+) -activated Cl(-) channel ANO1 by localized Ca(2+) signals. Jin X, Shah S, Du X, Zhang H, Gamper N.J Physiol. 2016 Jan 1;594(1):19-30. doi: 10.1113/jphysiol.2014.275107.
- Starving a Cell Promotes Airway Smooth Muscle Relaxation: Inhibition of Glycolysis Attenuates Excitation-Contraction Coupling. Xu S, Karmacharya N, Woo J, Cao G, Guo C, Gow A, Panettieri RA Jr, Jude JA. Am J Respir Cell Mol Biol. 2022 Oct 13. PMID: 36227725DOI: 10.1165/rcmb.2021-0495OC Online ahead of print.
- Metabolics in Asthma: A platform for discovery Xu S, Panettieri RA Jr., Jude J. Mol Aspects Med. 2022 Jun;85:100990. DOI: 10.1016/j.mam.2021.100990. Epub 2021 Jul 17. PMID: 34281719.
- Inhibition of ABCC1 Decreases cAMP Egress and Promotes Human Airway Smooth Muscle Cell Relaxation. DOI: 10.1165/rcmb.2021-0345OC.PMID: 34648729.
- Functional NMDA receptors are expressed by human pulmonary artery smooth muscle cells Dong YN, Hsu FC, Koziol-White CJ, Stepanova V, Jude J, Gritsiuta A, Rue R, Mott R, Coulter DA, Panettieri RA Jr, Krymskaya VP, Takano H, Goncharova EA, Goncharov DA, Cines DB, Lynch DR. Sci Rep. 2021 Apr 15;11(1):8205. doi: 10.1038/s41598-021-87667-0. PMID: 33859248.
- TGF-β: The missing link in obesity-associated airway diseases? Woo J, Koziol-White C, Panettieri RA Jr., Jude J. Curr Res Pharmacol Drug Discov. 2021 Feb 5;2:100016. doi: 10.1016/j.crphar.2021.100016. eCollection 2021. PMID: 34909651.
- FFAR1 activation attenuates histamine-induced myosin light chain phosphorylation and cortical tension development in human airway smooth muscle cells Xu S, Schwab A, Karmacharya N, Cao G, Woo J, Kim N, An SS, Panettieri RA Jr, Jude JA. . Respir Res. 2020 Nov 30;21(1):317.
- The odorant receptor OR2W3 on airway smooth muscle evokes bronchodilation via a cooperative chemosensory tradeoff between TMEM16A and CFTR Huang J, Lam H, Koziol-White C, Limjunyawong N, Kim D, Kim N, Karmacharya N, Rajkumar P, Firer D, Dalesio NM, Jude J, Kurten RC, Pluznick JL, Deshpande DA, Penn RB, Liggett SB, Panettieri RA, Dong X, An SS. . PNAS 2020 Oct 23. Online ahead of print.
- Role of CD38/cADPR signaling in obstructive pulmonary diseases Guedes AG, Dileepan M,Jude JA, Deshpande DA, Walseth TF, Kannan MS. Curr Opin Pharmacol. 2020 May 29;51:29-33. Online ahead of print.
- RGS4 promotes allergen- and aspirin-associated airway hyperresponsiveness by inhibiting PGE2 biosynthesis Wong GS, Redes JL, Balenga N, McCullough M, Fuentes N, Gokhale A, Koziol-White C,Jude JA, Madigan LA, Chan EC, Jester WH, Biardel S, Flamand N, Panettieri RA Jr, Druey KM. . J Allergy Clin Immunol. 2020 Mar 19:S0091-6749(20)30372-9. Online ahead of print.
- Salicylic acid amplifies Carbachol-induced bronchoconstriction in human precision-cut lung slices Jude J, Botelho D, Karmacharya N, Cao GY, Jester W, Panettieri RA Jr. Respir Res. 2019 Apr 11;20(1):72. doi: 10.1186/s12931-019-1034-x. PMID: 30971247 Free PMC article.