Education & Training
- Duquesne University, Pittsburgh PA B.S. 06/1982 Chemistry
- Duquesne University, Pittsburgh PA M.S. 06/1985 Pharmacology
- University of Pittsburgh School of Medicine, Pittsburgh PA Ph.D. 06/1992 Neuropharmacology
A. Personal Statement
I have extensive training in cell culture, immunocytochemical and calcium imaging techniques, applied to visceral and somatic systems as well as measurement of transmitter release. One of the most important discoveries involves my work on urinary bladder urothelium. While the urothelium, a specialized lining the urinary tract, has classically been thought of as a passive barrier to ion/solutes, we have uncovered a number of findings that lend support to the idea that these cells exhibit “neuron-like” properties. These properties include both a “sensor” function (i.e. expression of a number of sensor molecules that respond to temperature, mechanical and/or chemical stimuli) as well as a “transducer” function (release of various transmitters/mediators). Our findings revealed that the functional significance of a number of molecular targets in the bladder extends beyond pain sensation to include participation in normal bladder function. Thus, our pioneering work on properties of bladder urothelial cells has opened a new field and led to the suggestion that the urothelium deserves more attention as a potential target for treatment of painful bladder symptoms. My group also has evidence that the “transducer”, “sensor” and “barrier” properties of bladder urothelium are altered in a number of bladder pathologies such as overactive (idiopathic and neurogenic) bladder as well as in interstitial cystitis/bladder pain syndrome.
B. Positions and Employment
1992 Pharmaceutical Manufacturer’s Foundation Graduate Student Researcher,
Department of Pharmacology, University of Pittsburgh School of Medicine,
1992 International Research Fellow, Showa University, Tokyo, Japan
1992-1997 NIH NRSA Postdoctoral Fellow, UNC Chapel Hill Department of Physiology,
Chapel Hill, NC
1997 Instructor, Dept. Pharmacology, University of Pittsburgh School of Medicine,
1998 Research Assistant Professor of Pharmacology, University of Pittsburgh
School of Medicine
2001-2007 Assistant Professor of Medicine, Tenure Stream, University of Pittsburgh
School of Medicine
2007 Associate Professor of Medicine with Tenure, University of Pittsburgh
School of Medicine
2013 Professor of Medicine with Tenure, University of Pittsburgh School of Medicine
Honors and other professional activities:
1989 Graduate Student Award Center for Neuroscience University of Pittsburgh
1991 ASPET Graduate Student Travel Award
1992 NIH NRSA Postdoctoral Fellowship
2002 Recipient IUPHAR Young Investigator 1st Place Award
2002-present Editorial Board, American Journal of Physiology, Renal Physiology
2003 Senior Vice Chancellor Invited Presentation University of Pittsburgh
2003 APS Lazaro J. Mandel Young Investigator Award for research in
2003-present Section Editor, Neurourology and Urodynamics
2004 Participant, Neural Control Committee, WHO 3rd International Consultation
2005-2010 Executive Committee ASPET Division Systems/Integrative Pharmacology
2007 Plenary Speaker GlaxoSmithKline Urology Therapy Area Review
2008 Chair, Neural Control Committee, WHO 4th International Consultation
2009-15 University Pittsburgh DOM Representative to the Winters Foundation
2009 Member International Continence Society Scientific Executive Committee
2009 Chair Optimizing Animal Models for Translational Research Think Tank,
International Consultation on Incontinence-Research Society, Bristol UK
2009 Animal Models of Diabetic Complications Consortium (AMDCC)
2010 Keynote speaker, 17th Annual Neurogenic Bladder Meeting Yamanashi Japan
2010 Plenary Speaker Honoree 10th Annual Meeting Society for Interstitial Cystitis
2011 Chair, Think Tank, ‘How does the urothelium affect bladder/urethral function in
health and disease’; International Consultation on Incontinence-Research Society,
2011 Invited speaker, INComb-TRUST-SEA Joint European Urology Symposium
2012 Chair, Neural Control Committee, 5th International Consultation on Incontinence
2012-13 3rd International Consultation on Interstitial Cystitis Japan Executive Board
2010-14 External Advisor for INComb and TRUST European Consortiums
2013-15 Adjunct Professorship University of Antwerp (Belgium)
2013-17 Chair Basic Science Program-Society for Urology and Female Urodynamics
2016 Chair, Neural Control Committee, 6th International Consultation on Incontinence
C. Contribution to Science
1. One of the most important initial discoveries involved our work on the urinary bladder urothelium. While the urothelium, a specialized lining of the urinary tract, has classically been thought of as a passive barrier to ion/solutes, my laboratory has uncovered a number of novel findings that lend support to the idea that these cells exhibit ‘neuron-like’ properties. Our early publications provided evidence that urothelial cells exhibit functional ion channels/receptors and release of chemical mediators. These findings support specialized sensory and signaling properties that allow communication with neighboring cells including bladder nerves.
a) Birder LA, Apodaca G, de Groat WC and Kanai AJ. Adrenergic and capsaicin evoked nitric oxide release from urothelium and afferent nerves in urinary bladder. American Journal of Physiology 275:F226-229, 1998. PMID:9691011
b) Birder LA, Kanai AJ, de Groat WC, Kiss S, Nealen M.L., Burke N.E., Dineley K.E., Watkins S, Reynolds I.J., and Caterina M.J. Functional vanilloid receptors in non-neuronal urinary bladder epithelial cells. Proceedings of the National Academy of Sciences (USA) 98(23):13396-13401, 2001. PMID:11606761; PMCID:PMC60882.
c) Birder LA, Nakamura Y, Kiss S, Nealen M, Barrick S, Kanai AJ, Wang E, Ruiz G, de Groat WC, Apodaca G, Watkins S and Caterina MJ. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nature Neuroscience 5(9):856-890, 2002. PMID:12161756
d) Birder LA and de Groat WC. The Urothelium as a Sensory Organ. Nature Clinical Practice Urology, 4:46-54, 2007. PMID:17211425; PMCID:PMC3119256.
2. In addition to the contributions described above, my laboratory and collaborators also has shown the ‘transducer’, ‘sensor’ and ‘barrier’ properties of urothelium are altered in a number of bladderpathologies such as overactive bladder and bladder pain syndrome/interstitial cystitis, which presents with urgency, frequency and bladder pain. Our pioneering work on sensory properties of bladder urothelial cells has opened a new field and led to the suggestion that the urothelium deserves more attention as a potential target for treatment of a number of bladder dysfunctions including overactivity and pelvic pain. This body of work discusses how urothelial cells may receive and integrate multiple stimuli thus providing a ‘bidirectional link’ transferring information between the bladder and the nervous system.
a) Apodaca G, Kiss S, Ruiz WG, Meyers S, Zeidel M and Birder L. Disruption of bladder epithelium barrier function after spinal cord injury. American Journal of Physiology Renal Physiology 284: F966-976, 2003. PMID: 12527557
b) Chopra B, Barrick SR, Meyers S, Beckel JM, Zeidel ML, Ford AP, de Groat WC and Birder LA. Expression and function of bradykinin B1 and B2 receptors in normal and inflamed rat urinary bladder urothelium. Journal Physiology (London) 562:859-871, 2005. PMID:15576455; PMCID:PMC1665539.
c) Charrua A, Pinto R, Taylor A, Canelas A, Ribeiro-da-Silva A, Cruz CD, Birder LA and Cruz F. Can the adrenergic system be implicated in the pathophysiology of bladder pain syndrome/interstitial cystitis? A clinical and experimental study. Neurourology and Urodynamics, 34:489-96, 2015. PMID:24375689; PMCID: PMC4069202.
d) Birder LA and Andersson KE. Urothelial Signaling. Physiological Reviews, 93:653-80, 2013. PMID:23589830; PMCID:PMC3768101.
3. As changes in signaling/barrier function are not unique to the urinary bladder, we have begun to extend these observations to other types of epithelia. This is particularly relevant given the high incidence of associated diseases many of which share a change in epithelial function. Further, our studies have also examined the influence of additional factors (aging; ischemia; stress) that may contribute to patient symptoms in various bladder disorders. We also have expanded our understanding of mechanism of action underlying various treatment options (many of which target the uro-epithelium).
a) Wolf-Johnston AS, Hanna-Mitchell AT, Buffington CA, Shinde S, Roppolo JR, Mayer E and Birder LA. Alterations in the non-neuronal acetylcholine synthesis and release machinery in esophageal epithelium. Life Sciences 91:1065-9, 2012. PMID: 22569297; PMCID:PMC3435437.
b) Hanna-Mitchell AT, Wolf-Johnston AS, Barrick SR, Kanai AJ, Chancellor MB, de Groat WC and Birder LA. Effect of botulinum toxin A on urothelial-release of ATP and expression of SNARE targets within the urothelium. Neurourology and Urodynamics, 34:79-84, 2015. PMID:24167028; PMCID: PMC4035459.
c) Jiang Yuan-Hong, Liu Hsin-Tzu, Chuang Yao-Chi, Birder Lori, Chancellor MB and Kuo Hann-Chorng. Pilot study of liposome encapsulated onabotulinumtoxin A from patients with overactive bladder- a single center clinical results and changes of urothelial sensory proteins. Eur Urol 65:1117-24, 2014. PMID:24555904.
d) Hanna-Mitchell AT, Wolf-Johnston AS, Roppolo JR, Buffington CA and Birder LA. CRF family peptide signaling in feline bladder urothelial cells. Journal of Endocrinology 222:113-21, 2014. PMID:24829219; PMCID: PMC4137776.