Dr. Birder’s work has been durably funded by the NIH including a NIH MERIT award and currently two R01 grants studying bladder dysfunction with stress/pain and aging.  Her research has focused on the physiology and pharmacology of multiple organ systems in health and disease utilizing both in vivo and a number of in vitroapproaches.  For example, Dr. Birder and her team discovered that the epithelial cells that line the urinary bladder lumen (uro-epithelium) exhibits ‘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). These findings revealed that the functional significance of a number of molecular targets in certain types of epithelial- such as the lower urinary tract- extends beyond pain sensation to include participation in normal function. Thus, Dr. Birder’s 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 a number of urologic conditions.  Dr. Birder’s lab has also collaborated extensively in studies involving cellular bioenergetics, mitophagy and cellular communication using isolated mitochondria from the spinal cord, dorsal root ganglia, cardiac tissues and peripheral nerves.  Dr. Birder has also investigated the impact of aging and bladder pain on cellular homeostasis, which is likely to involve mitochondrial damage and increased oxidative stress and altered purine metabolism.  Evidence supporting purine dysregulation has been published by our team recently in JCI Insight (2020) and collaboration in the field of ophthalmology has revealed similar evidence of purine dysregulation in animal model for age-related macular degeneration and retinitis pigmentosa.  The most recent evidence has shown that targeting a single enzyme- PNPase- restores CIPN-associated purine dysregulation and resultant mitochondrial dysfunction/oxidative stress.  Taken together with expertise and research experience in cell biology and physiology, Dr. Birder is well suited to examine mechanisms underlying chronic visceral pain (bladder pain) including the validation of a novel target, PNPase.  Given the important and fundamental role for mitochondrial dysregulation in the pathogenesis of visceral pain conditions, therapies that can protect and restore mitochondria are likely to be important in terms of disease prevention. 

Highlighted Ongoing Projects

Contribution of Stress Induced Autonomic and Urothelial Dysregulation to IC/BPS

Principal Investigators:  Lori Birder, Ph.D. and Larissa Rodriguez. (Multi-PI) 

Agency:  NIH/NIDDK; Type: R01 DK115476; Period: 04/01/18-03/31/23

Goals: To examine the mechanisms underlying effect of chronic stress and increased sympathetic outflow on mitochondrial dysregulation and peripheral signaling in the context of bladder pain syndrome.

Bladder mucosal dysfunction during aging

Principal Investigators:  Lori A. Birder, Ph.D. (contact PI) and Gerard Apodaca, Ph.D. (MPI)

Agency:  NIH/NIA; Type:  1R01 AG056944-01; Period:  04/1/18-03/31/23

Goals:  To examine the effects of aging and oxidative stress on urothelial physiology and impact on cross-talk between urothelium and cells within the bladder wall.

Discovery of a novel, first-in-class endogenous small molecule potent and efficacious protective agent with restorative actions on retinal degeneration

Principal Investigator:  Yuanyuan Chen, PhD

Agency:  Bruce and Barbara Wiegand Entrepreneurial Research Award; Period: 09/01/2020-10/31/2022

Goals:  To examine impact of aging on associated retinal dysfunction.

Role: Co-investigator

Highlighted Citations:

Birder LA. Bladder Pain.  In: Neuro-Urology: Theory and Practice, Limin Liao and H. Madersbacher, eds., Springer, Dordrecht, 2019; doi.org/10.1007/978-94-017-7509-0.

Kullmann FA and Birder LA.  Role of neurogenic inflammation in local activity in visceral mucosa.  Seminars in immunopathology: neurogenic inflammation.  2018: doi:10.1007/s00281-018-0674-0.

Kullmann FA, McDonnell BM, Wolf-Johnston AS, Kanai AJ, Shiva S, Chelimsky T, Rodriguez L and Birder LA.  Stress-induced autonomic dysregulation of mitochondrial function in the rat urothelium.  Neurourology and Urodynamics 38:572-81, 2019. PMID:30575113.

Birder LA, Wolf-Johnston A, Wein AJ, Cheng F, Grove-Sullivan M, Kanai AJ, Watson AM, Stoltz D, Watkins SC, Robertson AM, Newman D, Dmochowski RR and Jackson EK.  Purine nucleoside phosphorylase inhibition ameliorates age-associated lower urinary tract dysfunctions.  Journal of Clinical Investigation Insight, 5(20): 140109, 2020. Doi:10.1172/jci.insight.140109.  PMCID: PMC7605521. PMID: 32910805.

B. Positions, Scientific Appointments and Honors

2022-26                                   Founding Editor-in-Chief ‘Continence’-the gold standard journal of the ICS

2020-23                                   Member Med7 Flanders Research Foundation (FWO) European Grant Review Board

2020-23                                   Member SUFU Executive Committee

2020-23                                   International Continence Society Board of Trustee Member

2020-                              Adjunct Professor, Dept Urology, SUNY Downstate College of Medicine, NY

2019-22                           American Urological Association (AUA) Research Advocacy Council Committee          

2019-                              Visiting Professor, Tor Vergata Universita Degli Studi di Roma

2018-             Associate Member UPSOM/UPMC Aging Institute

2018                                        Co- Scientific Chair International Continence Society Annual Meeting       

2018-21          Elected representative to the UPSOM Executive Committee of the Faculty

2017                                        Chair, Neural Control Committee, 6^th International Consultation on Incontinence

2013-17                           Chair Basic Science Program-Society for Urology and Female Urodynamics (SUFU)

2015-16         Co-guest ‘specialty’ editor: Autonomic nervous control of the urinary tract

2016                                        Co-Editor in chief on line journal ‘Bladder’

2013-15                          Adjunct Professorship University of Antwerp (Belgium)

2013                                Professor of Medicine with Tenure, University of Pittsburgh School of Medicine

2010-14                          External Advisor for INComb and TRUST European Consortiums          

2011                Invited speaker, INComb-TRUST-SEA Joint European Urology Symposium

2010                                        Keynote speaker 17^th annual Neurogenic Bladder meeting Yamanashi Japan

2009                                        Animal Models of Diabetic Complications Consortium (AMDCC) Steering Committee

2009                Chair Optimizing Animal Models for Translational Research Think Tank, International Consultation on Incontinence-Research Society, Bristol UK

2009-15                           University Pittsburgh DOM Representative to the Winters Foundation

2009                                        Member International Continence Society Scientific Executive Committee

2008                                        Chair, Neural Control Committee, WHO 4^th International Consultation on Incontinence

2007                                Associate Professor Medicine with Tenure, University of Pittsburgh School of Medicine

2007                                        Plenary Speaker GlaxoSmithKline Urology Therapy Area Review

2005-10                           Executive Committee ASPET Division Systems/Integrative Pharmacology

2001-07                                   Assistant Professor of Medicine, Tenure Stream, Univ of Pittsburgh School of Medicine

2000                Neural Control Committee, WHO 3^rd International Consultation on Incontinence

2003-21                       Section Editor, Neurourology and Urodynamics

2003                                        APS Lazaro J. Mandel Young Investigator Award for research in epithelial physiology

2003                            Senior Vice Chancellor Invited Presentation University of Pittsburgh

2002-08                       Editorial Board, American Journal of Physiology, Renal Physiology

2002                                       Recipient IUPHAR Young Investigator 1^st Place Award

1998                Assistant Professor of Pharmacology, University of Pittsburgh School of Medicine

1997                Instructor, Dept. Pharmacology, Univ of Pittsburgh School of Medicine, Pittsburgh, PA

1992-97          NIH NRSA Postdoctoral Fellow, UNC Chapel Hill Dept of Physiology, Chapel Hill, NC       

1992                                       NIH NRSA Postdoctoral Fellowship

1992                International Research Fellow, Showa University, Tokyo, Japan

1992                Pharmaceutical Manufacturer’s Foundation Graduate Student Researcher, Dept     Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA                            

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.

1. 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
2. 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
3. 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
4. Birder LA and de Groat WC.  The Urothelium as a Sensory Organ.  Nature Clinical Practice Urology, 4:46-54, 2007. PMID:17211425

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 bladder pathologies 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.

1. 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
2. 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
3. Birder LA, Wolf-Johnston AS, Sun Y and Chai TC. Alteration in TRPV1 and muscarinic (M3) receptor expression and function in idiopathic human overactive bladder urothelial cells. Acta Physiologica, 207:123-9, 2013. PMID:22691178
4. Birder LA and Andersson KE. Urothelial Signaling. Physiological Reviews, 93:653-80, 2013. PMID:23589830.

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).

1. 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
2. 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. European Urology 65:1117-24, 2014. PMID: 24555904.
3. 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.
4. 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, 2015. 34:79-84. PMID:24167028.

4. Chronic stress (including oxidative stress) can exacerbate symptoms in a number of urologic and co-morbid disorders.  My laboratory and collaborators have examined the impact of chronic psychological stress, traumatic spinal cord injury as well as aging and found these can result in significant alterations in mitochondrial health (both morphology and function), leading to increased reactive oxygen species (ROS) and oxidative stress/injury. Over time these changes can impact not only the urothelial barrier and signaling but impact bladder functions (and likely contribute to patient symptoms such as over/underactivity, pain, incontinence and even nocturia/nocturnal polyuria).  We have also found that treatments which can target the mitochondria and/or reduce ROS (antioxidants) can reverse or normalize these dysfunctions in biomechanical and signaling properties of the bladder. Also, we have recently shown that vasopressin receptors are expressed within the urinary bladder mucosa and this expression is increased with aging.

1. Truschel ST, Clayton DR, Beckel JM, Yabes JG, Yao Y, Wolf-Johnston A, Birder LA, Apodaca G.  Age-related endolysosome dysfunction in the rat urothelium.  PLoS One. 13(6):e0198817, 2018. PMID:29883476.
2. Kullmann FA, McDonnell BM, Wolf-Johnston AS, Kanai AJ, Shiva S, Chelimsky T, Rodriguez L and Birder LA.  Stress-induced autonomic dysregulation of mitochondrial function in the rat urothelium.  Neurourology and Urodynamics 38:572-81, 2019. PMID:30575113.
3. Birder LA, Van Kerrebroeck PEV.  Pathological mechanisms of nocturia and nocturnal polyuria: the contribution of cellular function, the urinary bladder urothelium, and circadian rhythm.  Urology. 2019.  Pii:S0090-4295(19)30683-1.  PMID:31369749.
4. Cheng F, Birder LA, Kullmann FA, Hornsby J, Watton PN, Watkins S, Thompson M, and Robertson AM.  Layer-dependent role of collagen recruitment during loading of the rat bladder wall. Biomechanical Modeling Mechanobiology 17:403-17, 2018. PMID: 29039043.

5. The purinergic nucleotide inosine is formed from the metabolism of adenosine.  Inosine has been shown to provide beneficial anti-inflammatory and protective effects to various target organ systems.  Remarkably, inosine has been shown to stimulate neural axonal outgrowth and improve sensory functions which is diminished with aging.  We have recently shown that changes in the enzyme purine nucleoside phosphorylase (PNPase) may reflect the extent of oxidative injury and cellular damage in a number of organ systems and conditions.  Blocking PNPase increases levels of ‘tissue-protective’ precursors (inosine) while simultaneously decreasing levels of ‘tissue-toxic’ hypoxanthine and xanthine (sources of ROS).  My laboratory and collaborators have shown that 8-aminoguanine (PNPase inhibitor) is protective to the aging lower urinary tract as well as other tissues that may be changed with age or injury.

1. Birder LA, Wolf-Johnston A, Wein AJ, Grove-Sullivan M, Stoltz D, Watkins S, Newman D, Dmochowski RR, Jackson EK.  A uro-protective agent with restorative actions on urethral and striated muscle morphology.  World J Urology 2020. Doi: 10.1007/s00345-020-03492-6.  PMCID: PMC8053723. PMID: 33078215.
2. Speich JE, Tarcan T, Hashtani H, Vahabi B, McCloskey KD, Andersson KE, Wein AJ and Birder LA.  Are oxidative stress and ischemia significant causes of bladder damage leading to lower urinary tract dysfunction?  Neurourology and Urodynamics, 2020, 3:S16-20, 2020.  PMID: 32056281
3. Birder LA, Wolf-Johnston A, Wein AJ, Cheng F, Grove-Sullivan M, Kanai AJ< Watson AM, Stoltz D, Watkins SC, Robertson AM, Newman D, Dmochowski RR and Jackson EK.  Purine nucleoside phosphorylase inhibition ameliorates age-associated lower urinary tract dysfunctions.  Journal of Clinical Investigation Insight, 5(20): 140109, 2020. Doi:10.1172/jci.insight.140109.  PMCID: PMC8053723. PMID: 33078215