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Overview

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.

The lab is exploring the disease physiologically and searching for a treatment through its proprietary murine model.

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).

Research Projects

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a debilitating chronic condition primarily affecting women. 3.2 to 7.9 million women over the age of 18 in the US suffer from IC/PBS. With no current effective treatments IC/PBS causes unrelenting bladder pain, frequent urination, and discomfort. Extreme cases show a huge impact on quality of life with patients having to urinate over 60 times a day and seven times throughout the night. Moreover, in several recent clinical trials, various compounds failed to show any promising effectiveness against IC/PBS. The direct and indirect costs for US IC/PBS patients and their families, including increased medical expenses and decreased work productivity, is estimated to be on the order of $21.1 billion dollars annually.

Key Factors in the Disease

Although the etiology of IC/PBS is poorly understood, a large body of literature implicates urothelial cell injury and mast cell activation as key factors in the pathogenesis of the disease. Pathologic studies have shown patient symptoms are correlated with lesions of the urothelium lining the bladder and the accumulation of mast cells throughout all layers. Contributing mechanisms include deficiencies in the glycosaminoglycan (GAG) layer of the bladder and mast cell-mediated neuro-inflammation.

Lab Model

The Oottamasathien laboratory has developed a mouse model of inflammatory cystitis that is physiologically relevant, biologically based, non-infectious, non-chemically induced, and recapitulates key clinical aspects of IC/PBS using the natural catheliciden (LL-37). Through this model we have shown that LL-37 induces cystitis, both acutely and chronically, with severity of inflammation being dose dependent. After a single insult of LL-37, bladders demonstrated severe inflammation with global erythema, hemorrhage, edema and hypervascularity.

Our most recent work has implicated mast cells as a key cell type in driving both inflammation and pain in our LL-37 induced bladder injury model. Our model has also yielded prolonged pain responses to be independent of acute inflammation, more closely mimicking what has been observed in patients with IC/PBS. In addition, our patented SAGE compounds have been demonstrated to substantially attenuate both inflammation and pain, and may represent a new class of non-opioid based analgesics for future therapeutic use. Finally, recent work with innovative thermosensitive biopolymers have demonstrated a more sustained delivery system of therapeutics to target organs of interest.

Additional Studies

Further mechanistic studies are being performed to hopefully one day fully understand and elucidate the entire mechanistic role LL-37 plays in IC/PBS, both acutely and chronically. Our lab is making great headway in understanding and treating IC/PBS, bridging the gap between bench top to bedside.

Research Positions

Our lab is currently in search of post-doctoral MD or MD/PhD research candidates and senior research associates. Email Dr. Oottamasathien to learn more.

Publications

Amniotic therapeutic biomaterials in urology: current and future applications.

Oottamasathien S, Hotaling JM, Craig JR, Myers JB, Brant WO.

Transl Androl Urol. 2017 Oct;6(5):943-950. doi: 10.21037/tau.2017.09.01. Review.

PMID: 29184795

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

Combination of Extracorporeal Shockwave Lithotripsy and Ureteroscopy for Large Staghorn Calculi in a Pediatric Patient: Case Report.

Schults AJ, Jia W, Ost MC, Oottamasathien S.

J Endourol Case Rep. 2017 May 1;3(1):64-66. doi: 10.1089/cren.2017.0029. eCollection 2017.

PMID: 28616590

Silk-elastinlike protein polymers enhance the efficacy of a therapeutic glycosaminoglycan for prophylactic treatment of radiation-induced proctitis.

Jensen MM, Jia W, Isaacson KJ, Schults A, Cappello J, Prestwich GD, Oottamasathien S, Ghandehari H.

J Control Release. 2017 Oct 10;263:46-56. doi: 10.1016/j.jconrel.2017.02.025. Epub 2017 Feb 21.

PMID: 28232224

Childhood Cancer Risk in the Siblings and Cousins of Men with Poor Semen Quality.

Anderson RE, Hanson HA, Lowrance WT, Redshaw J, Oottamasathien S, Schaeffer A, Johnstone E, Aston KI, Carrell DT, Cartwright P, Smith KR, Hotaling JM.

J Urol. 2017 Mar;197(3 Pt 2):898-905. doi: 10.1016/j.juro.2016.09.110. Epub 2017 Jan 26.

PMID: 28131504

Prevention of sinonasal inflammation by a synthetic glycosaminoglycan.

Pulsipher A, Qin X, Thomas AJ, Prestwich GD, Oottamasathien S, Alt JA.

Int Forum Allergy Rhinol. 2017 Feb;7(2):177-184. doi: 10.1002/alr.21865. Epub 2016 Nov 11.

PMID: 27863138

Topical cathelicidin (LL-37) an innate immune peptide induces acute olfactory epithelium inflammation in a mouse model.

Alt JA, Qin X, Pulsipher A, Orb Q, Orlandi RR, Zhang J, Schults A, Jia W, Presson AP, Prestwich GD, Oottamasathien S.

Int Forum Allergy Rhinol. 2015 Dec;5(12):1141-50. doi: 10.1002/alr.21634. Epub 2015 Sep 8.

PubMed PMID: 26346056

LL-37 induced cystitis and the receptor for advanced glycation end-products (RAGE) pathway.

Roundy LM, Jia W, Zhang J, Ye X, Prestwich GD, Oottamasathien S.

Adv Biosci Biotechnol. 2013 Aug 1;4(8B):1-8.

PubMed PMID: 24883227

Physiological relevance of LL-37 induced bladder inflammation and mast cells.

Oottamasathien S, Jia W, Roundy LM, Zhang J, Wang L, Ye X, Hill AC, Savage J, Lee WY, Hannon AM, Milner S, Prestwich GD.

J Urol. 2013 Oct;190(4 Suppl):1596-1602. doi: 10.1016/j.juro.2013.01.002. Epub 2013 Jan 9.

PubMed PMID: 23313203

Prevention of Anti-microbial Peptide LL-37-Induced Apoptosis and ATP Release in the Urinary Bladder by a Modified Glycosaminoglycan.

Lee WY, Savage JR, Zhang J, Jia W, Oottamasathien S, Prestwich GD, Thumbikat P, ed.

PLoS ONE. 2013;8(10):e77854. doi:10.1371/journal.pone.0077854.

PMC: 3813730

A murine model of inflammatory bladder disease: cathelicidin peptide induced bladder inflammation and treatment with sulfated polysaccharides.

Oottamasathien S, Jia W, McCoard L, Slack S, Zhang J, Skardal A, Job K, Kennedy TP, Dull RO, Prestwich GD.

J Urol. 2011 Oct;186(4 Suppl):1684-92. doi: 10.1016/j.juro.2011.03.099. Epub 2011 Aug 19.

PubMed PMID: 21855919

Padded self-adhesive strap immobilization following newborn bladder exstrophy closure: the Utah straps.

Wallis MC, Oottamasathien S, Wicher C, Hadley D, Snow BW, Cartwright PC

J Urol. 2013 Dec;190(6):2216-20. doi: 10.1016/j.juro.2013.06.041. Epub 2013 Jun 26.

PubMed PMID: 23810641

Pediatric urinary stone composition in the United States.

Gabrielsen JS, Laciak RJ, Frank EL, McFadden M, Bates CS, Oottamasathien S, Hamilton BD, Wallis MC.

J Urol. 2012 Jun;187(6):2182-7. doi: 10.1016/j.juro.2012.01.124. Epub 2012 Apr 12.

PubMed PMID: 22503021

Parameatal urethral cysts in prepubertal males.

Willis HL, Snow BW, Cartwright PC, Wallis MC, Oottamasathien S, deVries C.

J Urol. 2011 Mar;185(3):1042-5. doi: 10.1016/j.juro.2010.10.038. Epub 2011 Jan 19. Review.

PubMed PMID: 21247599

Metastatic Crohn's disease of the penis in a pediatric patient.

Pohl JF, Comstock JM, Oottamasathien S.

Inflamm Bowel Dis. 2011 Apr;17(4):1056. doi: 10.1002/ibd.21408.

PubMed PMID: 20645314

250 consecutive unilateral extravesical ureteral reimplantations in an outpatient setting.

Wicher C, Hadley D, Ludlow D, Oottamasathien S, Wallis MC, Devries C, Snow BW, Cartwright PC.

J Urol. 2010 Jul;184(1):311-4. doi: 10.1016/j.juro.2010.01.056. Epub 2010 May 20.

PubMed PMID: 20488495

Temporal-spatial protein expression in bladder tissue derived from embryonic stem cells.

Thomas JC, Oottamasathien S, Makari JH, Honea L, Sharif-Afshar AR, Wang Y, Adams C, Wills ML, Bhowmick NA, Adams MC, Brock JW 3rd, Hayward SW, Matusik RJ, Pope JC 4th.

J Urol. 2008 Oct;180(4 Suppl):1784-9. doi: 10.1016/j.juro.2008.03.098. Epub 2008 Aug 21.

PubMed PMID:18721943

Prostate epithelial cell fate.

Matusik RJ, Jin RJ, Sun Q, Wang Y, Yu X, Gupta A, Nandana S, Case TC, Paul M, Mirosevich J, Oottamasathien S, Thomas J.

Differentiation. 2008 Jul;76(6):682-98. doi: 10.1111/j.1432-0436.2008.00276.x. Epub 2008 May 7. Review.

PubMed PMID: 18462434

Urothelial inhibition of transforming growth factor-beta in a bladder tissue recombination model.

Oottamasathien S, Williams K, Franco OE, Wills ML, Thomas JC, Sharif-Afshar AR, DeMarco RT, Brock JW 3rd, Bhowmick NA, Hayward SW, Pope JC 4th.

J Urol. 2007 Oct;178(4 Pt 2):1643-9. Epub 2007 Aug 16.

PubMed PMID: 17707033

Testicular tumours in children: a single-institutional experience.

Oottamasathien S, Thomas JC, Adams MC, DeMarco RT, Brock JW 3rd, Pope JC 4th.

BJU Int. 2007 May;99(5):1123-6.

PubMed PMID: 17437431

Directed differentiation of embryonic stem cells into bladder tissue.

Oottamasathien S, Wang Y, Williams K, Franco OE, Wills ML, Thomas JC, Saba K, Sharif-Afshar AR, Makari JH, Bhowmick NA, DeMarco RT, Hipkens S, Magnuson M, Brock JW 3rd, Hayward SW, Pope JC 4th, Matusik RJ.

Dev Biol. 2007 Apr 15;304(2):556-66. Epub 2007 Jan 12.

PubMed PMID: 17289017

Primary extrarenal nephroblastomatosis.

Oottamasathien S, Wills ML, Brock JW 3rd, Pope JC 4th.

Urology. 2007 Jan;69(1):184.e3-4.

PubMed PMID: 17270650

Bladder tissue formation from cultured bladder urothelium.

Oottamasathien S, Williams K, Franco OE, Thomas JC, Saba K, Bhowmick NA, Staack A, Demarco RT, Brock JW 3rd, Hayward SW, Pope JC 4th.

Dev Dyn. 2006 Oct;235(10):2795-801.

PubMed PMID: 16804891

Gonadoblastoma and Turner syndrome.

Brant WO, Rajimwale A, Lovell MA, Travers SH, Furness PD 3rd, Sorensen M, Oottamasathien S, Koyle MA.

J Urol. 2006 May;175(5):1858-60.

PubMed PMID: 16600779

Laparoscopic Palomo varicocele ligation in children and adolescents: results of 103 cases.

Koyle MA, Oottamasathien S, Barqawi A, Rajimwale A, Furness PD 3rd.

J Urol. 2004 Oct;172(4 Pt 2):1749-52; discussion 1752.

PubMed PMID: 15371805

Recent advances in hormonal therapy for advanced prostate cancer.

Oottamasathien S, Crawford ED.

Oncology (Williston Park). 2003 Aug;17(8):1047-52; discussion 1054-8. Review.

PubMed PMID: 12966672