Bio

Academic Appointments


Honors & Awards


  • Best Poster (MP33-12 Voiding Efficiency Following Correction Bladder Outlet Obstruction in Women), AUA 2018 Annual Meeting, San Francisco, CA. (2018 (5/19))
  • Early-Career Investigators Showcase (Pelvic Irradiation Induces Two Phenotypes - OAB vs UAB), AUA 2018 Annual Meeting, San Francisco, CA. (2018 (5/19))
  • Research Travel Award (Radiation Induced Bladder Dysfunction in the Rat), Basic Sciences Symposium. AUA 2017 Annual Meeting. Boston, MA. (2017 (5/12))
  • Best Clinical Research Award (Isometric Detrusor Reserve Predicts Spontaneous Void after TURP), Congress of Urologic Research and Education on Aging Underactive Bladder (CURE-UAB), Washington D.C. (2017 (3/9))
  • Travel Scholarship. CURE-UAB 2017 Meeting., Congress of Urologic Research and Education on Aging Underactive Bladder (CURE-UAB), Washington D.C. (2017 (3/9))
  • Spectrum KL2 Scholar, Stanford Clinical and Translational Science Award (2016-2018), Stanford University School of Medicine, Stanford, CA (2016 (7/1))
  • Best Resident Research Award (2014 - 2015), Albany Medical Center, Div. of Urology, Albany, NY (2015 (06/19))
  • 1st Place National Chief Resident Debate (Bladder Exstrophy: Argument for Modern Staged Repair), American Urological Association, 2015 Annual Meeting, New Orleans, LA (2015 (05/17))
  • Best Resident Teaching Award (2013 - 2014), Albany Medical Center, Div. of Urology, Albany, NY (2014 (06/20))
  • 2nd Place Resident Debate (Orchiopexy Retractile Testicle: Argument for Surgery), Northeast Section American Urological Association, 65th Annual Meeting, Saratoga Springs, NY (2013 (11/02))
  • 2nd Place Prize Essay Contest (Model of pelvic floor dysfunction after pelvic floor stimulation), Northeast Section American Urological Association, 65th Annual Meeting, Saratoga Springs, NY (2013 (11/01))
  • Best Resident Research Award (2012 - 2013), Albany Medical Center, Div. of Urology, Albany, NY (2013 (06/21))
  • 3rd Place Basic Science Competition (Loss renal protein phosphatase obstructive uropathy), 18th Annual Urology Resident Research Day, Skaneateles, NY (2013 (04/20))
  • 1st Place Prize Essay Contest (PPM1A and TGF-beta/SMAD signalling obstructive uropathy), Northeast Section American Urological Association, 64th Annual Meeting, Niagara Falls, Ontario (2012 (09/14))
  • 1st Place Resident Debate (Acute versus Delayed Prosthesis after Priapism), 17th Annual Urology Resident Research Day, Skaneateles, NY (2012 (04/21))

Boards, Advisory Committees, Professional Organizations


  • Member, American Urological Association (2011 - Present)
  • Member, Society of Women in Urology (2011 - Present)
  • Member, GLMA (2014 - Present)
  • Member, WPATH (2015 - Present)
  • Member, International Continence Society (2016 - Present)
  • Education Committee, International Continence Society (2016 - Present)

Professional Education


  • Fellowship:Stanford University Dept of Urology (2017) CA
  • Residency:Albany Medical College Urologic Surgery Residency (2015) NY
  • Residency:Albany Medical College General Surgery Residency (2011) NY
  • Medical Education:University of North Carolina School of Medicine (2010) NC
  • Bachelor of Science, North Carolina State University (2004)

Research & Scholarship

Current Research and Scholarly Interests


Dr. Amy Dobberfuhl, received a B.S. in Mechanical Engineering from North Carolina State University in 2004 and her M.D. from the University of North Carolina at Chapel Hill School of Medicine in 2010. She completed her residency training in Urology at Albany Medical College in New York in 2015. She then completed an ACGME fellowship in FPMRS (Neurourology & Voiding Dysfunction) in the Department of Urology at Stanford University in 2017. Following fellowship Dr. Dobberfuhl was appointed the faculty research position of Instructor in the Department of Urology 7/1/2017 and her practice includes both a clinical and research focus.

Dr. Dobberfuhl's current clinical focus includes: Pelvic Reconstruction, Neurourology, and Voiding Dysfunction.

Dr. Dobberfuhl?s current research focus includes: basic science, clinical and translational research in overactive / underactive bladder and radiation cystitis; urine biomarkers of compensated and decompensated detrusor dysfunction; animal models of voiding and pelvic floor dysfunction; pharmacologic modulation of lower urinary tract function and fibrosis. Dr. Dobberfuhl?s past basic science and clinical research interests have included: animal models of voiding and pelvic floor dysfunction (mouse, rat, rabbit); renal fibrosis and molecular cell signaling inflammatory pathways; pelvic floor ischemia; neuroanatomy and bladder tissue mechanics.

Dr. Dobberfuhl's basic science and clinical translational research efforts for 2016-2018 were supported by the Stanford Clinical and Translation Science Award to Spectrum (NIH KL2 TR 001083). To complement her KL2 sponsored research activities and translational research goals, she is obtaining an M.S. in Epidemiology and Clinical Research, anticipated 2018. Through a CIRM grant (2016-2017), in collaboration with Dr. Bertha Chen (PI), her laboratory is currently investigating a novel iPSC pSMC stem cell therapy for the treatment of radiation cystitis, project titled "Prevention of the Late Stage Adverse Effects of Radiation on the Bladder using Human Induced Pluripotent Stem Cells in a Rat Model of Radiation Cystitis". Through a SUFU grant (2015-2017), Dr. Dobberfuhl's research has explored the physiologic effect of the various onabotulinumtoxinA chemodenervation injection patterns in use today, project titled "Localization of OnabotulinumtoxinA and Cystometric Response Following Single versus Multiple Injections for the Treatment of Overactive Bladder in a Rat Model". Upcoming activities include a patient oriented research proposal to investigate the basic science mechanisms of underactive bladder and the creation of a benign urologic urine bio-repository for the identification of urine biomarkers of compensated and decompensated detrusor dysfunction. In collaboration with her basic science colleagues Dr. Bertha Chen (Urogynecology) and Dr. Edward Diaz (Pediatric Urology), Dr. Dobberfuhl's additional laboratory activities include exploring novel pharmacologic targets which may modulate lower urinary tract function and fibrosis.

Projects


  • Localization of OnabotulinumtoxinA and Cystometric Response Following Single versus Multiple Injections for the Treatment of Overactive Bladder in a Rat Model, Stanford University School of Medicine (11/9/2015 - Present)

    2015 SUFU Foundation Study of Chemodenervation

    Location

    Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA

  • Recovery of Bladder Contractile Function after Correction of Bladder Outlet Obstruction in Men and Women (8/14/2015 - 7/31/2018)

    Location

    Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA

  • Long Term Durability of Third Line Treatments for Refractory Overactive Bladder in Men and Women (8/14/2015 - 7/31/2018)

    Location

    Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA

  • Estrogen Replacement Reduces Oxidative Stress and Restores Bladder and Pelvic Floor Contractile Function in an Animal Model of Menopause and Tissue Ischemia

    Location

    Stratton VA Medical Center, Albany, NY

  • A Novel Model of Pelvic Organ Ischemia: Pelvic Floor Contractile Function is More Resistant to Ischemia and Post-Ischemia Reperfusion than Bladder Detrusor Muscle

    Location

    Stratton VA Medical Center, Albany, NY

  • Our 10-Year Experience with Female Urethrolysis: Urethral Pressure Profilometry Correlates with Degree of Obstruction in Clinically Obstructed Women after Anti-Incontinence Procedure

    Location

    Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA

  • Isometric Detrusor Contractile Reserve Predicts Immediate Recovery of Spontaneous Voiding after Transurethral Resection of Prostate

    Location

    Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA

  • Spontaneous Voiding is Surprisingly Recoverable via Outlet Procedure after Documented Underactive Bladder on Urodynamics

    Location

    Albany Medical College, Albany, NY

  • Prevention of the Late Stage Adverse Effects of Radiation on the Bladder using Human Induced Pluripotent Stem Cells in a Rat Model of Radiation Cystitis

    Location

    Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA

  • Postop recovery of underactive bladder (UAB) detrusor function after transurethral resection of prostate (TURP) in men

    Location

    Albany Medical College, Albany, NY

Lab Affiliations


Teaching

Graduate and Fellowship Programs


Publications

All Publications


  • Peroxisome proliferator-activated receptor gamma agonist as a novel treatment for interstitial cystitis: A rat model. Investigative and clinical urology Mahal, A., Young-Lin, N., Dobberfuhl, A., Estes, J., Comiter, C. V. 2018; 59 (4): 257?62

    Abstract

    Purpose: To understand the therapeutic potential of pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist with a propensity to cause bladder mucosal proliferation, on interstitial cystitis (IC) in a rat model.Materials and Methods: Using a previously described animal model for IC, Sprague-Dawley rats were treated with biweekly cyclophosphamide injections (35 mg/kg) to induce cystitis. Animals were divided into 4 groups (n=6 for each group): IC plus daily sham saline gavage (IC+Pio-), IC plus daily pioglitazone gavage (15 mg/kg) (IC+Pio+), normal rats with daily pioglitazone (IC-Pio+), and normal rats with neither IC nor pioglitazone (IC-Pio- or Control). At the end of four weeks, urinary frequency and bladder capacity were measured. Histologic examination of urothelial integrity was also performed.Results: Average voids per hour were significantly lower in IC+Pio+ (4.01.9) vs. IC+Pio- (10.02.4) rats (p<0.01) and were similar to IC-Pio+ (6.01.4) and IC-Pio- (6.01.5) controls. Cystometric capacity was significantly higher in IC+Pio+ (0.9450.122 mL) vs. IC+Pio- rats (0.5880.165 mL, p=0.01) and was comparable to IC-Pio- capacity (0.8170.196 mL) and IC-Pio+ capacity (0.9410.188 mL). Urothelial structural integrity was improved in IC+Pio+ rats versus IC+Pio- rats upon histologic observation.Conclusions: Pioglitazone, a PPAR-gamma agonist, improved bladder function in cyclophosphamide-induced cystitis by both observed urinary frequency and measured cystometric capacity. Urothelial structural integrity was also improved. Pioglitazone, due to a propensity to cause bladder mucosal proliferation, may prove useful for treating IC, and deserves further investigation.

    View details for DOI 10.4111/icu.2018.59.4.257

    View details for PubMedID 29984341

  • THE NATURAL HISTORY OF RADIATION CYSTITIS IN A RAT MODEL OF ACUTE AND CHRONIC LOWER URINARY TRACT DYSFUNCTION Dobberfuhl, A. D., Briggs, M. A., Wen, Y., Ning, S., Graves, E. E., Diaz, E. C., Chen, B. WILEY. 2018: S538
  • CHARACTERIZATION OF RELAXIN RECEPTOR EXPRESSION IN HUMAN BLADDER SMOOTH MUSCLE CELLS AND EVALUATION OF ITS EFFECT ON TISSUE REMODELING AND FIBROSIS Diaz, E., Briggs, M., Wen, Y., Dobberfuhl, A., Chen, B. WILEY. 2018: S533
  • A Systematic Approach to the Evaluation and Management of the Failed Artificial Urinary Sphincter. Current urology reports Dobberfuhl, A. D., Comiter, C. V. 2017; 18 (3): 18-?

    Abstract

    In men with post-prostatectomy incontinence, persistent or recurrent urinary leakage following artificial urinary sphincter placement is a frustrating complaint. Surgical failure can be classified as occurring early in the post-operative period vs. late-following a period of established continence-and should be managed according to the time course and severity of urinary leakage. We present a systematic approach for the evaluation and treatment of the failed artificial urinary sphincter. After considering the patient's individualized treatment goals and impact on quality of life, the clinician can more appropriately advise patients on a management strategy for their recurrent or persistent urinary incontinence following artificial urinary sphincter placement.

    View details for DOI 10.1007/s11934-017-0666-y

    View details for PubMedID 28233225

  • Chapter 9: Uterosacral Ligament Vaginal Vault Suspension Native Tissue Repair for Incontinence and Prolapse Dobberfuhl, A. D., De, E. J. Springer International Publishing. 2017: 131?142
  • Loss of expression of protein phosphatase magnesium-dependent 1A during kidney injury promotes fibrotic maladaptive repair FASEB JOURNAL Samarakoon, R., Rehfuss, A., Khakoo, N. S., Falke, L. L., Dobberfuhl, A. D., Helo, S., Overstreet, J. M., Goldschmeding, R., Higgins, P. J. 2016; 30 (10): 3308-3320

    Abstract

    Protein phosphatase magnesium-dependent-1A (PPM1A) dephosphorylates SMAD2/3, which suppresses TGF-? signaling in keratinocytes and during Xenopus development; however, potential involvement of PPM1A in chronic kidney disease is unknown. PPM1A expression was dramatically decreased in the tubulointerstitium in obstructive and aristolochic acid nephropathy, which correlates with progression of fibrotic disease. Stable silencing of PPM1A in human kidney-2 human renal epithelial cells increased SMAD3 phosphorylation, stimulated expression of fibrotic genes, induced dedifferentiation, and orchestrated epithelial cell-cycle arrest via SMAD3-mediated connective tissue growth factor and plasminogen activator inhibitor-1 up-regulation. PPM1A stable suppression in normal rat kidney-49 renal fibroblasts, in contrast, promoted a SMAD3-dependent connective tissue growth factor and plasminogen activator inhibitor-1-induced proliferative response. Paracrine factors secreted by PPM1A-depleted epithelial cells augmented fibroblast proliferation (>50%) compared with controls. PPM1A suppression in renal cells further enhanced TGF-?1-induced SMAD3 phosphorylation and fibrotic gene expression, whereas PPM1A overexpression inhibited both responses. Moreover, phosphate tensin homolog on chromosome 10 depletion in human kidney-2 cells resulted in loss of expression and decreased nuclear levels of PPM1A, which enhanced SMAD3-mediated fibrotic gene induction and growth arrest that were reversed by ectopic PPM1A expression. Thus, phosphate tensin homolog on chromosome 10 is an upstream regulator of renal PPM1A deregulation. These findings establish PPM1A as a novel repressor of the SMAD3 pathway in renal fibrosis and as a new therapeutic target in patients with chronic kidney disease.-Samarakoon, R., Rehfuss, A., Khakoo, N. S., Falke, L. L., Dobberfuhl, A. D., Helo, S., Overstreet, J. M., Goldschmeding, R., Higgins, P. J. Loss of expression of protein phosphatase magnesium-dependent 1A during kidney injury promotes fibrotic maladaptive repair.

    View details for DOI 10.1096/fj.201500105R

    View details for Web of Science ID 000384329800005

    View details for PubMedID 27328942

  • A Novel Cystometric Model of Pelvic Floor Dysfunction After Rabbit Pelvic Floor Noxious Electrical Stimulation FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY Dobberfuhl, A. D., Spettel, S., Schuler, C., Dubin, A. H., Levin, R. M., De, E. J. 2016; 22 (4): 248-253

    Abstract

    Although a relationship between pelvic floor dysfunction and lower urinary tract symptoms is described in the literature, the mechanism and pathways need further characterization. We developed an animal model of pelvic floor dysfunction after noxious stimulation of the pubococcygeus (PC) muscle.Fifteen female adult rabbits were evaluated with cystometry (CMG) and electromyography (EMG) recordings from the PC muscle. Cystometry/EMG was performed before and after treatment animal (n = 11) received noxious pelvic floor electrical stimulation through the PC EMG electrode, and controls (n = 4) underwent sham needle placement. Two animals underwent S3 dorsal rhizotomy to demonstrate that the observed results required afferent innervation.Voiding changes were demonstrated in 9 of 11 rabbits after stimulation. Most of the rabbits (7/9) exhibited a prolonged-dysfunctional voiding pattern with larger capacity (mean, 17 mL [SEM, 8 mL]), longer intercontractile interval (227% [SEM, 76%]) and duration (163% [SEM, 20%]), and increased postvoid residual (24 mL [SEM, 6 mL]). The remaining dysfunctional rabbits (2/9) exhibited an overactive-dysfunctional voiding pattern with lower capacity (-26 mL [SEM, 6 mL]), shortened intercontractile interval (16% [SEM, 9%]) and duration (56% [SEM, 30%]), and decreased postvoid residual (-27 mL [SEM, 6 mL]). Nonresponder rabbits (2/11) were relatively unchanged in their micturition cycles after stimulation. Rhizotomy animals were acontractile and filled until overflow incontinence occurred.Using noxious electrical stimulation of the pelvic musculature, we were able to produce an animal model of pelvic floor dysfunction in most rabbits as hallmarked by a larger bladder capacity, an increased intercontractile interval, and prolonged contraction duration.

    View details for DOI 10.1097/SPV.0000000000000253

    View details for Web of Science ID 000378713200013

    View details for PubMedID 26829345

  • The artificial urinary sphincter and male sling for postprostatectomy incontinence: Which patient should get which procedure? Investigative and clinical urology Comiter, C. V., Dobberfuhl, A. D. 2016; 57 (1): 3-13

    Abstract

    Surgery is the most efficacious treatment for postprostatectomy incontinence. The ideal surgical approach depends on a variety of patient factors including history of prior incontinence surgery or radiation treatment, bladder contractility, severity of leakage, and patient expectations. Most patients choose to avoid a mechanical device, opting for the male sling over the artificial urinary sphincter. The modern male sling has continued to evolve with respect to device design and surgical technique. Various types of slings address sphincteric incompetence via different mechanisms of action. The recommended surgery, however, must be individualized to the patient based on degree of incontinence, detrusor contractility, and urethral compliance. A thorough urodynamic evaluation is indicated for the majority of patients, and the recommendation for an artificial urinary sphincter, a transobturator sling, or a quadratic sling will depend on urodynamic findings and the patient's particular preference. As advancements in this field evolve, and our understanding of the pathophysiology of incontinence and mechanisms of various devices improves, we expect to see continued evolution in device design.

    View details for DOI 10.4111/icu.2016.57.1.3

    View details for PubMedID 26966721

  • Initial Evaluation and Management of Acute Urinary Retention AUA Update Series Dobberfuhl, A. D., Comiter, C. V. 2016; 35: 95-104
  • Noxious electrical stimulation of the pelvic floor and vagina induces transient voiding dysfunction in a rabbit survival model of pelvic floor dystonia. Korean journal of urology Dobberfuhl, A. D., Spettel, S., Schuler, C., Levin, R. M., Dubin, A. H., De, E. J. 2015; 56 (12): 837-844

    Abstract

    Existing data supports a relationship between pelvic floor dysfunction and lower urinary tract symptoms. We developed a survival model of pelvic floor dysfunction in the rabbit and evaluated cystometric (CMG), electromyographic (EMG) and ambulatory voiding behavior.Twelve female adult virgin rabbits were housed in metabolic cages to record voiding and defecation. Anesthetized CMG/EMG was performed before and after treatment animals (n=9) received bilateral tetanizing needle stimulation to the pubococcygeous (PC) muscle and controls (n=3) sham needle placement. After 7 days all animals were subjected to tetanizing transvaginal stimulation and CMG/EMG. After 5 days a final CMG/EMG was performed.Of rabbits that underwent needle stimulation 7 of 9 (78%) demonstrated dysfunctional CMG micturition contractions versus 6 of 12 (50%) after transvaginal stimulation. Needle stimulation of the PC musculature resulted in significant changes in: basal CMG pressure, precontraction pressure change, contraction pressure, interval between contractions and postvoid residual; with time to 3rd contraction increased from 38 to 53 minutes (p=0.008 vs. prestimulation). Vaginal noxious stimulation resulted in significant changes in: basal CMG pressure and interval between contractions; with time to 3rd contraction increased from 37 to 46 minutes (p=0.008 vs. prestimulation). Changes in cage parameters were primarily seen after direct needle stimulation.In a majority of animals, tetanizing electrical stimulation of the rabbit pelvic floor resulted in voiding changes suggestive of pelvic floor dysfunction as characterized by a larger bladder capacity, longer interval between contractions and prolonged contraction duration.

    View details for DOI 10.4111/kju.2015.56.12.837

    View details for PubMedID 26682025

  • Female stress urinary incontinence and the mid-urethral sling: Is obstruction necessary to achieve dryness? WORLD JOURNAL OF UROLOGY Dobberfuhl, A. D., De, E. J. 2015; 33 (9): 1243-1250

    Abstract

    Recently, the American Urogynecologic Society and Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction released position statements on the use of mid-urethral slings. The statement offers that the polypropylene mesh mid-urethral sling (retropubic and transobturator) is now the recognized worldwide standard of care for the surgical treatment of stress urinary incontinence. The purpose of the current manuscript is to examine whether the polypropylene mesh mid-urethral sling should be the standard of care.Data for this review were acquired by a systematic search of the medical literature.The Trial of Mid-Urethral Slings found that retropubic and transobturator slings were associated with a significant rate of adverse events, despite being comprised of surgeons from high-volume, experienced centers. Stress urinary incontinence is not just a urethral disease due to intrinsic sphincteric deficiency. It can also be related to urethral hypermobility, which in turn is caused by anterior vaginal wall laxity. Often both hypermobility and intrinsic sphincter deficiency coexist. Recognizing the role of anterior vaginal wall support is important to understanding the role of procedures (such as Burch or needle suspension procedures) which have the potential of correcting stress incontinence without affecting voiding parameters.As a discipline, we need to conceptualize stress incontinence due to urethral hypermobility or intrinsic sphincter deficiency as separate entities and design our procedures to restore the underlying suspected pathology.

    View details for DOI 10.1007/s00345-015-1600-x

    View details for Web of Science ID 000360509100005

    View details for PubMedID 26025190

  • Loss of tumour suppressor PTEN expression in renal injury initiates SMAD3-and p53-dependent fibrotic responses JOURNAL OF PATHOLOGY Samarakoon, R., Helo, S., Dobberfuhl, A. D., Khakoo, N. S., Falke, L., Overstreet, J. M., Goldschmeding, R., Higgins, P. J. 2015; 236 (4): 421-432

    Abstract

    Deregulation of the tumour suppressor PTEN occurs in lung and skin fibrosis and diabetic and ischaemic renal injury. However, the potential role of PTEN and associated mechanisms in the progression of kidney fibrosis is unknown. Tubular and interstitial PTEN expression was dramatically decreased in several models of renal injury, including aristolochic acid nephropathy (AAN), streptozotocin (STZ)-mediated injury and ureteral unilateral obstruction (UUO), correlating with Akt, p53 and SMAD3 activation and fibrosis. Stable silencing of PTEN in HK-2 human tubular epithelial cells induced dedifferentiation and CTGF, PAI-1, vimentin, ?-SMA and fibronectin expression, compared to HK-2 cells expressing control shRNA. Furthermore, PTEN knockdown stimulated Akt, SMAD3 and p53(Ser15) phosphorylation, with an accompanying decrease in population density and an increase in epithelial G1 cell cycle arrest. SMAD3 or p53 gene silencing or pharmacological blockade partially suppressed fibrotic gene expression and relieved growth inhibition orchestrated by deficiency or inhibition of PTEN. Similarly, shRNA suppression of PAI-1 rescued the PTEN loss-associated epithelial proliferative arrest. Moreover, TGF?1-initiated fibrotic gene expression is further enhanced by PTEN depletion. Combined TGF?1 treatment and PTEN silencing potentiated epithelial cell death via p53-dependent pathways. Thus, PTEN loss initiates tubular dysfunction via SMAD3- and p53-mediated fibrotic gene induction, with accompanying PAI-1-dependent proliferative arrest, and cooperates with TGF?1 to induce the expression of profibrotic genes and tubular apoptosis.

    View details for DOI 10.1002/path.4538

    View details for Web of Science ID 000358302900004

    View details for PubMedID 25810340

  • Identification of CNS Neurons Innervating the Levator Ani and Ventral Bulbospongiosus Muscles in Male Rats JOURNAL OF SEXUAL MEDICINE Dobberfuhl, A. D., Oti, T., Sakamoto, H., Marson, L. 2014; 11 (3): 664-677

    Abstract

    The pelvic striated muscles play an important role in mediating erections and ejaculation, and together these muscles compose a tightly coordinated neuromuscular system that is androgen sensitive and sexually dimorphic.To identify spinal and brains neurons involved in the control of the levator ani (LA) and bulbospongiosus (BS) in the male adult and preadolescent rat.Rats were anesthetized, and the transsynaptic retrograde tracer pseudorabies virus (PRV) was injected into the LA muscle of adults or the ventral BS muscle in 30-day-old rats. After 3-5 days rats were sacrificed, and PRV-labeled neurons in the spinal cords and brains were identified using immunohistochemistry. The presence of gastrin-releasing peptide (GRP) in the lumbar spinal neurons was examined.The location and number of PRV-labeled neurons in the spinal cord and brain and GRP colocalization in the lumbar spinal cord.PRV-labeled spinal interneurons were found distributed throughout T11-S1 of the spinal cord, subsequent to dorsal medial motoneuron infection. The majority of spinal interneurons were found in the lumbosacral spinal cord in the region of the dorsal gray commissure and parasympathetic preganglionic neurons. Preadolescent rats had more PRV-labeled spinal interneurons at L5-S1 where the motoneurons were located but relatively less spread rostrally in the spinal cord compared with adults. Lumbar spinothalmic neurons in medial gray of L3-L4 co-localized PRV and GRP. In the brain consistent labeling was seen in areas known to be involved in male sexual behavior including the ventrolateral medulla, hypothalamic paraventricular nucleus, and medial preoptic area.Common spinal and brain pathways project to the LA and BS muscles in the rat suggesting that these muscles act together to coordinate male sexual reflexes. Differences may exist in the amount of synaptic connections/neuronal pathways in adolescents compared with adults.

    View details for DOI 10.1111/jsm.12418

    View details for Web of Science ID 000332140300006

    View details for PubMedID 24373488

  • Evaluation & Treatment of Overactive Bladder AUA University: Core Curriculum Dobberfuhl, A. D., De, E. J. American Urological Association. 2014
  • Induction of renal fibrotic genes by TGF-beta 1 requires EGFR activation, p53 and reactive oxygen species CELLULAR SIGNALLING Samarakoon, R., Dobberfuhl, A. D., Cooley, C., Overstreet, J. M., Patel, S., Goldschmeding, R., Meldrum, K. K., Higgins, P. J. 2013; 25 (11): 2198-2209

    Abstract

    While transforming growth factor-? (TGF-?1)-induced SMAD2/3 signaling is a critical event in the progression of chronic kidney disease, the role of non-SMAD mechanisms in the orchestration of fibrotic gene changes remains largely unexplored. TGF-?1/SMAD3 pathway activation in renal fibrosis (induced by ureteral ligation) correlated with epidermal growth factor receptor(Y845) (EGFR(Y845)) and p53(Ser15) phosphorylation and induction of disease causative target genes plasminogen activator inhibitor-1 (PAI-1) and connective tissue growth factor (CTGF) prompting an investigation of the mechanistic involvement of EGFR and tumor suppressor p53 in profibrotic signaling. TGF-?1, PAI-1, CTGF, p53 and EGFR were co-expressed in the obstructed kidney localizing predominantly to the tubular and interstitial compartments. Indeed, TGF-?1 activated EGFR and p53 as well as SMAD2/3. Genetic deficiency of either EGFR or p53 or functional blockade with AG1478 or Pifithrin-?, respectively, effectively inhibited PAI-1and CTGF induction and morphological transformation of renal fibroblasts as did SMAD3 knockdown or pretreatment with the SMAD3 inhibitor SIS3. Reactive oxygen species (ROS)-dependent mechanisms initiated by TGF-?1 were critical for EGFR(Y845) and p53(Ser15) phosphorylation and target gene expression. The p22(Phox) subunit of NADPH oxidase was also elevated in the fibrotic kidney with an expression pattern similar to p53 and EGFR. EGF stimulation alone initiated, albeit delayed, c-terminal SMAD3 phosphorylation (that required the TGF-?1 receptor) and rapid ERK2 activation both of which are necessary for PAI-1 and CTGF induction in renal fibroblasts. These data highlight the extensive cross-talk among SMAD2/3, EGFR and p53 pathways essential for expression of TGF-?1-induced fibrotic target genes.

    View details for DOI 10.1016/j.cellsig.2013.07.007

    View details for Web of Science ID 000324971800013

    View details for PubMedID 23872073

  • Ureteral Obstruction-Induced Renal Fibrosis: An In Vivo Platform for Mechanistic Discovery and Therapeutic Intervention. Cell & developmental biology Dobberfuhl, A. D., Samarakoon, R., Higgins, C. E., Mian, B. M., Overstreet, J. M., Higgins, S. P., Kogan, B. A., Higgins, P. J. 2012; 1 (3)

    View details for DOI 10.4172/2168-9296.1000e107

    View details for PubMedID 23264954

    View details for PubMedCentralID PMC3526117

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