Overview

The Department of Urology at Massachusetts General Hospital is a recognized leader in investigating the causes of prostate and bladder cancer and developing preventative methods, treatments and cures for various urological diseases and disorders, such as bladder dysfunction, Benign prostatic hyperplasia (BPH), and interstitial cystitis/painful bladder syndrome (IC/PBS). For patients who do not respond to conventional treatments, our clinical trials can offer a promising (albeit investigative) treatment option.

Urologic diseases and conditions affect people of all ages and can lead to a decrease in quality of life. Non-cancerous urologic diseases affect many individuals:

  • More than 15 million people in the U.S. have urinary incontinence
  • 14 percent of people in the U.S. suffer from chronic kidney disease
  • BPH is common condition in men older than age 50
  • IC/PBS affects over three million women above the age of 18 in the US

There has been a rise in the prevalence of urologic cancers, which is estimated at 19.5 percent of cancers globally. Most urologic cancers are kidney, prostate, testicular and bladder cancers, with prostate cancer being the most prevalent. 

There is a significant need for new scientific insights into urologic conditions to inform the advancement of new therapies and earlier diagnosis.

Our studies investigate:

  • The molecular basis of urologic tumors, including cancers of the prostate, bladder and kidney
  • Basic mechanisms responsible for common urologic diseases
  • The causes of urological disorders and diseases in patients
  • Protein biomarkers found in the urine of patients with bladder and prostate cancer to develop diagnostic tests
  • The differences between therapy-resistant and receptive prostate cancer cells
  • The molecular mechanisms of bladder dysfunction associated with type 2 diabetes
  • Mechanisms responsible for prostate gland growth in BPH
  • Inflammatory cascade for better care and treatment of those suffering from IC/PBS

Team

Aria Olumi, MD
Director, Urology Research
Co-director, GU Oncology Clinical Program
Program Director, Urology Residency


Adam S. Feldman, MD, MPH
Urologist, Department of Urology
Director, Combined Harvard Urologic Oncology Fellowship


Chin-Lee Wu, MD, PhD
Associate Director, Genitourinary Pathology Services
Associate Pathologist


Siam Oottamasathien, MD, FAAP, FACS
Director of Pediatric Urology Basic Science Research, Massachusetts General Hospital for Children Division of Pediatric Urology
Associate Professor of Surgery/Pediatric Urology, Harvard Medical School


Shulin Wu, MD, PhD
Director, Urology Research Laboratory
Pathologist


Zongwei Wang, PhD, Instructor in Surgery


Sharron X. Lin, PhD,
Instructor, Harvard Medical School


Rongbin Ge, MD, PhD, Senior Investigator


Wanjian Jia, MD, PhD, Research Associate


Libing Hu, MD, Visiting Research Scholar


Cyrus Rassoulian, Undergraduate Student


Jonathan Pham, Graduate Student


Research Projects

5-alpha reductase 2 (5-AR2) is a Key Enzyme Responsible for Proper Development of Prostate Tissue

Inhibition of 5-AR2 has proven to be efficacious for management of urinary symptoms associated with benign prostatic hyperplasia (BPH). However, some patients are resistant to the therapeutic effects of 5-AR2 inhibitor for management of lower urinary tract symptoms. The laboratory of Aria Olumi, MD, has shown that 30 percent of benign human prostate samples did not express the 5-AR 2 protein. They have demonstrated that the promoter region of 5AR2 contains a CpG island that is methylated in benign prostate epithelial cells and in 39 percent of benign human prostate samples. Methylation of the 5AR2 promoter may account for low or absent expression of 5AR2 in human adult prostate tissues.

Publications:

Wang Z, Hu L, Salari K, Bechis S, Ge R, Wu S, Rassoulian C, Pham J, Wu CL, Tabatabaei S, Douglas SW, Olumi AF. Androgenic to estrogenic switch in human adult prostate gland is regulated by epigenetic silencing of steroid 5α-reductase 2. J Pathol. 2017 Sep 20. PMID: 28940538

Ge R, Wang Z, Bechis S, Otsetov A, Hua S, We S, Wu C, Tabatabaei S, Olumi A. DNA Methyl Transferase 1 Reduces Expression of 5-alpha Reductase 2 in the Aging Adult Prostate. Am J Pathol, 2015 Mar;185(3):870-82. PMID: 25700986

Bechis SK, Otsetov AG, Ge R, Wang Z, Vangel MG, Wu CL, Tabatabaei S, Olumi AF. Age and Obesity Promote Methylation and Suppression of 5-Alpha Reductase 2- Implications for Personalized Therapy in Benign Prostatic Hyperplasia. Journal of Urology, 2015; 194:1031-7. PMID: 25916673

Molecular Mechanisms of Bladder Dysfunction Associated with Type 2 Diabetes

Diabetes mellitus (DM) affects seven percent of the US population. DM patients often have urologic symptoms such as voiding, recurrent urinary tract infections and erectile dysfunction. Diabetic bladder dysfunction is a common complication and affects up to 80 percent of patients with diabetes. The laboratory of Aria Olumi, MD, is conducting research aimed at identifying molecular changes that are responsible for diabetic bladder cystopathy, which causes bladder dysfunction, to help identify diabetic patients at risk of developing bladder dysfunction prior to presentation of the late stages of the disease. The lab is also evaluating the molecular pathways that lead to diabetic cystopathy to improve our understanding of bladder dysfunction, and help devise preventive strategies for secondary complications associated with type 2 diabetes.

Publications:

Wang Z, Cheng Z, Cristofaro V, Li J, Xiao X, Gomez P, Ge R, Gong E, Strle K, Sullivan M, Adam R, White M, and Olumi AF. Inhibition of TNF-α improves the bladder dysfunction that is associated with type 2 diabetes in mice. Diabetes, 2012, 61(8):2134-45. PMID: 22688336 

Genetic Expression Profiles Associated with Prostate Cancer

The laboratory of Chin-Lee Wu, MD, PhD, is using laser capture microdissection and DNA microarray techniques to identify a 32-gene signature whose expression can be used to predict prostate cancer outcomes. A continuous risk index was developed that assesses individualized recurrence risk. The 32-gene risk index was validated in an independent, blinded set of post-radical prostatectomy tissue samples. The lab is now developing a new gene-based diagnostic test to guide clinical management of prostate cancer. The genes identified in this study may also be used as new therapeutic targets.

Publications:

Development and validation of a 32-gene prognostic index for prostate cancer progression. Wu CL, Schroeder BE, Ma XJ, Cutie CJ, Wu S, Salunga R, Zhang Y, Kattan MW, Schnabel CA, Erlander MG, McDougal WS. Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6121-6. PMC3625257

News:

Gene-expression signature may signify risk for recurrence, metastasis in prostate cancer

Metabolomic Signature of Prostate Cancer

There is a clinical need to improve the method for imaging prostate cancer in vivo. In collaboration with Dr. Leo Cheng, Mass General Pathology and Radiology, the laboratory of Chin-Lee Wu has identified a metabolomic signature of prostate cancer. The lab is applying this signature in the development of an in vivo imaging technique for prostate cancer to help detect, localize and quantify prostate cancer.

Publications:

DeFeo EM, Wu CL, McDougal WS, Cheng LL. A decade in prostate cancer: from NMR to metabolomics. Nat Rev Urol. 2011 May 17;8(6):301-11. PMID: 21587223

Wu CL, Jordan KW, Ratai EM, Sheng J, Adkins CB, Defeo EM, Jenkins BG, Ying L, McDougal WS, Cheng LL. Metabolomic imaging for human prostate cancer detection. Sci Transl Med. 2010 Jan 27;2(16):16ra8. PMC2857699

Kaul D, Wu CL, Adkins CB, Jordan KW, Defeo EM, Habbel P, Peterson RT, McDougal WS, Pohl U, Cheng LL. Assessing prostate cancer growth with mRNA of spermine metabolic enzymes. Cancer Biol Ther. 2010 May 1;9(9):736-42. PMID: 20215859

Androgen Receptor Co-activators Involved in Prostate Cancer

Most prostate cancer death is due to the development of androgen independence. The androgen receptor is responsible for cell growth in both androgen dependent and independent prostate cancers. The laboratory of Chin-Lee Wu, PhD, MD, has identified two novel androgen receptor co-activators that may be involved in the development of androgen independence in prostate cancer. Characterizing these androgen receptor co-activators may lead to new drug targets for androgen independent prostate cancer.

Publications:

Development and validation of a 32-gene prognostic index for prostate cancer progression. Wu CL, Schroeder BE, Ma XJ, Cutie CJ, Wu S, Salunga R, Zhang Y, Kattan MW, Schnabel CA, Erlander MG, McDougal WS. Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6121-6. PMC3625257

Inflamatory pathways of interstitial cystitis/painful bladder syndrome

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a debilitating chronic condition that affects 3.2 to 7.9 million women above the age of 18 in the US. IC/PBS causes unrelenting bladder pain, frequent urination and discomfort. Currently, there are no effective treatments for this chronic, life-altering condition. The Oottamasathien Laboratory at Massachusetts General Hospital is focused on understanding the inflammatory cascade for better care and treatment of those suffering from IC/PBS. Specifically, the Oottamasathien lab is examining the antimicrobial properties of cathelicidin (LL-37) and its potential to initiate the inflammatory cascade response. The team is researching its mechanistic role in IC/PBS and discovering how to inhibit the inflammatory cascade by limiting LL-37 mediated bladder inflammation, fibrosis and pain. In addition, the group is exploring potent anti-inflammatory and non-opioid analgesic therapeutics based on a unique and patented sulfated glycosaminoglycan (SAGE).

Publications:

Bladder pain in an LL-37 interstitial cystitis and painful bladder syndrome model. Jia W, Schults AJ, Jensen MM, Ye X, Alt JA, Prestwich GD, Oottamasathien S. Am J Clin Exp Urol. 2017 Sep 1;5(2):10-17. eCollection 2017. PMID: 29034266

Alt JA, Qin X, Pulsipher A, Orb Q, Orlandi RR, Zhang J, Schults A, Jia W, Presson AP, Prestwich GD, Oottamasathien S.  Topical cathelicidin (LL-37) an innate immune peptide induces acute olfactory epithelium inflammation in a mouse model.  Int Forum Allergy Rhinol.  2015 Dec;5(12):1141-50. doi: 10.1002/alr.21634. Epub 2015 Sep 8. PubMed PMID: 26346056

Research Laboratories

Urology Research Labs:

Laboratory of Chin-Lee Wu, MD, PhD
Dr. Wu's lab studies the molecular basis of urologic tumors, including cancers of the prostate, bladder and kidney.


Laboratory of Aria Olumi, MD
The aim of Dr. Olumi's lab is to reduce the burden on our patients by studying the basic mechanisms that are responsible for some of the common urologic diseases.


Laboratory of Siam Oottamasathien, MD, FAAP, FACS
The Oottamasathien Laboratory at Massachusetts General Hospital is focused on understanding the inflammatory cascade for better care and treatment of those suffering from IC/PBS.

Clinical Research

The Department of Urology has several ongoing clinical research projects that investigate the causes of urological disorders and potential treatments for these diseases.

Bladder and Prostate Cancer Biomarkers

This project aims to identify predictive biomarkers for prostate and bladder cancer. Researchers are analyzing various proteins found in the urine of patients with bladder and prostate cancer to identify unique proteins that may be used to diagnose bladder or prostate cancer in patients. Several candidate proteins have been identified. If successful, a simple urine test could replace invasive biopsies to diagnose patients. We also are examining whether various tumor markers can predict treatment outcomes.

Urinary Bladder Cancer Visualization Devices

Investigators are developing devices that can create a 3-D map of the urinary bladder in cancer patients to determine blood vessel concentration below the surface of the bladder – a harbinger of tumor development. Researchers also hope to develop a visual system to determine nerve function of the bladder.

Urinary Stone Disease

The Department of Urology has many clinical research projects focused on the prevention and treatment of stone disease. We have compiled a database of over 7,500 patients who have undergone surgical intervention since 1995. Our physicians are investigating:

  • Metabolic risk factors involved in stone disease
  • Implications and prevention of infections in stone disease patients
  • Prevention of stone recurrence through diet and other measures
  • Use of advanced imaging technology including state-of-the-art techniques to enhance identification of stone composition, while limiting the potential harm of radiation
  • Use of a polymer to prevent stone migration during surgical procedures, developed at Mass General

Erectile Dysfunction

The Department of Urology is conducting clinical research on erectile dysfunction and the restoration of nerve endings that may be injured during radical prostatectomy. We are currently evaluating the use of nerve growth factors to restore erectile function in patients who had their nerves injured or removed during radical prostatectomy.

Diabetes and Urinary Dysfunction

Diabetes affects 10 percent of the U.S. population, and urologic issues associated with diabetes are common. Unfortunately, urologic complications related to diabetes are poorly understood and inadequately studied. We have developed a model that recapitulates the signs and symptoms of diabetes detected in humans. This model serves as an excellent starting point to investigate the urologic complications associated with diabetes. Genetic studies are also being conducted to improve our understanding of these complications. With the information gained from these studies, we aim to reduce the suffering of urologic complications that many diabetes patients experience.

Publications:

Inhibition of TNF-α improves the bladder dysfunction that is associated with type 2 diabetes in mice. Wang Z, Cheng Z, Cristofaro V, Li J, Xiao X, Gomez P, Ge R, Gong E, Strle K, Sullivan M, Adam R, White M, and Olumi AF. Diabetes, 2012, 61(8):2134-45. PMID: 22688336 

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