Highlights

Focus on Urology

Combating Urological Conditions

Urology Department

In the Department of Urology at Children’s, knowledge of urological tissues and access to a large patient population are paving the way for innovative therapies and diagnostics.

Under the direction of David Diamond, MD, urologist-in-chief, clinicians and researchers in the Department of Urology at Boston Children’s Hospital, are working to provide a new basic understanding of the genitourinary tract, which has been poorly studied in comparison to other organ systems. As the largest pediatric urology service in the world, the department performs 3,100 surgical procedures and cares for 18,000 children each year. The team’s fundamental knowledge of urological tissues and its access to a large patient population is paving the way for innovative therapies for a variety of common and rare illnesses affecting patients.

Carlos Estrada, M.D.

Silk-based Tissue Engineering Method for Bladder Repair

In addition to his clinical responsibilities, Carlos Estrada, MD, assistant in Urology, is conducting cutting-edge tissue engineering research with a focus on bladder repair. Recent regenerative medicine approaches using conventional biomaterials, the patients’ own smooth muscle cells and the cells lining the bladder have had some success. Dr. Estrada and Joshua Mauney, PhD, research fellow in Urology, have shown that silk scaffolds support bladder augmentation and the maintenance of organ functionality in a defect mouse model. Silk is thought to provide an exceptional combination of physical characteristics that are well suited to support bladder function and are readily amenable to modifications that encourage appropriate degradation and integration into host tissue. Drs. Estrada and Mauney are currently working on moving their technology into large animal models and focusing on optimizing the ideal source of cells for the bladder augmentation. TIDO is looking for an industry partner to help move this technology forward.

References

Stem cells: a review and implications for urology. Yu RN, Estrada CR. Urology. 2009 Dec 4. PMID: 19963239

Caliceal diverticula in children: natural history and management. Estrada CR, Datta S, Schneck FX, Bauer SB, Peters CA, Retik AB. J Urol. 2009 Mar;181(3):1306-11 PMID: 19152936

Richard Lee, M.D.

Novel Urinary Markers of Urinary Tract Obstruction and Vesicoureteral Reflux

The research interests of Richard Lee, MD, assistant in Urology, are in the field of urinary proteomics and biomarker discovery. In particular, Dr. Lee is focusing on identifying clinically significant urinary markers of urinary tract obstruction (UTO) and vesicoureteral reflux (VUR). Currently, five to seven percent of all prenatal ultrasounds identify findings consistent with possible UTO or VUR. Unfortunately, there are no appropriate guidelines or indicators to determine which children are at risk for renal damage or who should be tested, and postnatal tests are invasive and involve radiation. These biomarkers will be helpful in determining which children with these conditions require either surgical or medical intervention or observation. Through his research, Dr. Lee has developed a translational platform for discovery based quantitative urinary proteomics. Additionally, through his clinical interactions, he has assembled a unique pediatric urinary specimen repository. TIDO is looking for a development partner to translate this discovery into a product for the benefit of patients.

References:

Robot-assisted laparoscopic nephrectomy and contralateral ureteral reimplantation in children. Lee RS, Sethi AS, Passerotti CC, Peters CA. J Endourol. 2009 Dec 3. PMID: 19958154

Proteomics and opportunities for clinical translation in urological disease. Vaezzadeh AR, Steen H, Freeman MR, Lee RS. J Urol. 2009 Sep;182(3):835-43. PMID: 19616261

Biomarkers for pediatric urological disease. Lee RS. Curr Opin Urol. 2009 Jul;19(4):397-401. PMID: 19440151

Rosalyn Adam, Ph.D.

Growth Factor Function in Prostate and Bladder Conditions

Rosalyn Adam, PhD, associate director of Urology Research, studies growth factor function and mechanical signaling in urologic diseases. She and her colleagues have identified novel functions for heparin-binding epidermal growth factor-like growth factor in prostate and bladder cancers. Dr. Adam is also interested in understanding the regulation of gene expression in bladder smooth muscle cells exposed to mechanical stretch and growth factor stimulation. These studies relate to the mechanisms underlying pathologic remodeling of the bladder wall that leads to voiding dysfunction. Dr. Adam and Aruna Ramachandran, PhD, post doctoral fellow in Urology, have recently shown distension-induced expression of thrombomodulin in a rat model of bladder stretch injury and have shown for the first time, the ability of thrombomodulin to regulate smooth muscle cell migration, a hallmark of smooth muscle remodeling. Their ultimate goal is to identify critical signaling pathways that could be potential targets for therapeutics. Dr. Adam is interested in industry sponsored research with a company working in the field of urology.

References

Rapid preparation of nuclei-depleted detergent-resistant membrane fractions suitable for proteomics analysis. Adam RM, Yang W, Di Vizio D, Mukhopadhyay NK, Steen H. BMC Cell Biol. 2008 Jun 5;9:30. PMID: 18534013

GATA-6 mediates human bladder smooth muscle differentiation: involvement of a novel enhancer element in regulating alpha-smooth muscle actin gene expression. Kanematsu A, Ramachandran A, Adam RM. Am J Physiol Cell Physiol. 2007 Sep;293(3):C1093-102. Epub 2007 Jul 11. PMID: 17626241

Cholesterol sensitivity of endogenous and myristoylated Akt. Adam RM, Mukhopadhyay NK, Kim J, Di Vizio D, Cinar B, Boucher K, Solomon KR, Freeman MR. Cancer Res. 2007 Jul 1;67(13):6238-46. PMID: 17616681

Jordan Dimitrakov, M.D., Ph.D.

Diagnostic Markers for Urologic Chronic Pelvic Pain Syndrome

Urologic chronic pelvic pain syndrome (UCPPS) is a debilitating condition characterized by recurring pain in the bladder and the surrounding pelvic region, often accompanied by voiding and sexual dysfunction. Currently there are 12 million men and women in the U.S. with UCPPS, yet there are no reliable, definitive diagnostic tests available. Since other conditions can produce similar symptoms, UCPPS is currently diagnosed by using an exclusion method. Jordan Dimitrakov, MD, PhD, staff scientist in Urology, and colleagues have identified 16 proteins that are differentially expressed in the urine and serum samples of patients with UCPPS. These proteins have the potential to become diagnostic and therapeutic biomarkers for this condition. This technology could be translated into a non-invasive lab test to diagnose and then adequately treat patients with UCPPS. TIDO has built a patent portfolio around these markers and an exclusive license is available.

References:

p53 mediates interstitial cystitis antiproliferative factor (APF)-induced growth inhibition of human urothelial cells. Kim J, Keay SK, Dimitrakov JD, Freeman MR. FEBS Lett. 2007 Aug 7;581(20):3795-9. Epub 2007 Jul 2. PMID: 17628545

Drug delivery systems in urology--getting "smarter". Farokhzad OC, Dimitrakov JD, Karp JM, Khademhosseini A, Freeman MR, Langer R. Urology. 2006 Sep;68(3):463-9. PMID: 17010721

Management of chronic prostatitis/chronic pelvic pain syndrome: an evidence-based approach. Dimitrakov JD, Kaplan SA, Kroenke K, Jackson JL, Freeman MR. Urology. 2006 May;67(5):881-8. PMID: 16698346

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