Moalli Research Group
Principal Investigator:
Pam Moalli, MD, PhD
Dr. Moalli's research is in the general area of pelvic floor disorders such as pelvic organ prolapse and urinary incontinence. The multidisciplinary lab has taken four main approaches to investigating this understudied disease. First, the lab determined that the ratio of collagens decreases in the vaginal supportive connective tissues of postmenopausal women not on hormone therapy (HT), resulting in inferior biomechanical properties.
The altered collagen ratios are primarily due to a decrease in collagen I relative to collagen III. Using in vivo assays to test the biomechanical properties of the vagina and its supportive tissues of the rodent, the lab showed that the functional endpoint of the biochemical changes associated with a lack of hormones is inferior tissue biomechanical properties. Studies on human tissues demonstrated that when prolapse is advanced (stage III or greater), connective tissue remodeling is accelerated and hormones lose their protective effect.
A second area of interest is defining the impact of hormones on the progression of pelvic organ prolapse in the presence of mechanical stretch. Building upon research from a previous grant, which demonstrated the negative impact menopause can have on the vagina and supportive tissues, the lab has introduced an additional variable – mechanical stretch.
Specifically, the lab is interested in the response of the vagina and supportive connective tissues to the mechanical burden imposed by disrupted support and the mechanism by which estrogen and progesterone modify this response. The hypothesis is that injury to the vagina and/or its supportive tissues at the time of vaginal birth alters the transmission of mechanical loads to these structures, thereby altering the stimulus to resident connective tissue fibroblasts and modifying their biological response.
The third area of interest is defining the mechanisms of maternal birth injury using a multidisciplinary approach. Dr. Moalli hypothesizes that specific functional adaptations must take place within the vagina to afford passage of the fetus with minimal maternal injury. In the event that these adaptations are exceeded or incomplete, maternal injury ensues. This early injury contributes to the development of pelvic floor dysfunction later in life. The lab aims to define the adaptations of the vagina in pregnancy to achieve vaginal delivery and to determine how birth injury can impact tissue recovery using a rodent and primate model. The lab also plans to develop preventative strategies to maximize vaginal distension and reduce maternal trauma at the time of vaginal birth.
The lab’s fourth area of study is the comprehensive evaluation of prolapse meshes by an interdisciplinary research team. There is growing evidence that the complications associated with prolapse meshes cause unacceptably high rates of morbidity including infection, mesh shrinkage, mesh erosion, mesh exposure, pelvic, rectal, and bladder pain, and dyspareunia. Dr. Moalli established an interdisciplinary team of scientists to comprehensively test previously or newly marketed prolapse meshes and to develop the next generation of graft materials based on specific scientific criteria.
Having determined how biochemical and structural changes in the prolapsed vagina impact passive and active mechanical behavior, the team hypothesizes that the shortcoming of current prolapse meshes is that they are too stiff. By implanting commonly used synthetic prolapse meshes into the vagina of nonhuman primates with prolapse using the gold standard surgical procedure (the abdominal sacrocolpopexy), the lab is able to define the cellular, biochemical and biomechanical impact on the vagina at six months post-implantation. The lab also explores the development of future grafts for prolapse surgery.
Lab Members
Wenjun Zong, MD, PhD, Research Instructor
Department of Obstetrics, Gynecology & Reproductive Sciences
University of Pittsburgh
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Projects include: The study of hormones, mechanical stretch, tissue remodeling, proteasome pathways, and MMP regulation in vaginal and vaginal supportive tissues.
Suzan Stein, BS
Laboratory Technician and Study Coordinator
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Projects include: The study of MMP activity, immunohistochemistry, and histology in vaginal and vaginal supportive tissues.
Steven Abramowitch, PhD
Assistant Professor
Department of Bioengineering
Department of Obstetrics, Gynecology & Reproductive Sciences
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Andrew Feola, BS
Graduate Student
University of Pittsburgh Bioengineering department
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Project: Studying the restoration of the biomechanical properties of the prolapsed vagina using synthetic graft materials
Zegbeh Jallah, BS
Graduate Student, University of Pittsburgh Bioengineering department
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Project: Studying the mechanisms of mechanotransduction in the female pelvic floor
Jonathon Shepherd, MD, MS
Fellow, Female Pelvic Medicine and Reconstructive Pelvic Surgery
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Project: Studying the biomechanical properties of synthetic graft materials
Laura Skoczylas, MD
Fellow, Female Pelvic Medicine and Reconstructive Pelvic Surgery
Email
Project: Studying smooth muscle contractility in the rat vagina
Lab Alumni
Marianna Alperin, MD, MSCR
Attending Urogynecologist, Kaiser Permanente, East Los Angeles
Grace Chen, MD
Attending Urogynecologist, Johns Hopkins University
James Daucher, MD, MSCR
Attending Urogynecologist, Howard University
Kristen Debes, BS
Medical Student, Philadelphia College of Osteopathic Medicine
Robert Duerr, BS
Medical Student, University of Miami
Susan Gordy Street, RN
University of Pittsburgh Medical Center
Nancy Howden, MD
Attending Urogynecologist, University of North Carolina
Keisha Jones, MD, MSCR
Attending Urogynecologist, Tufts University
Jerry Lowder, MD, MS
Attending Urogynecologist, University of Pittsburgh
Dan Moon, MS
Medical Student, Drexel University
Jennifer Navarro, MD
Attending Urogynecologist, University of Florida
Noah Papas, MS
Johnson and Johnson
Vivian Sung, MD
Attending Urogynecologist, Brown University
Lindsay Tallarico, MD
Resident in Urogynecology, University of Pittsburgh
Selected Publications
- Jones KA, Feola A, Meyn L, Abramowitch SD, & Moalli PA. Tensile properties of commonly used prolapse meshes. Int Urogynecol J Pelvic Floor Dysfunct, 20(7):847-53, Jul. 2009.
- Abramowitch SD, Feola A, Jallah Z, & Moalli PA. Tissue mechanics, animal models, and pelvic organ prolapse: a review. Eur J Obstet Gynecol Reprod Biol, 144 Suppl 1:S146-58, May 2009.
- Zong W, Meyn LA, & Moalli PA. The amount and activity of active matrix metalloproteinase 13 is suppressed by estradiol and progesterone in human pelvic floor fibroblasts. Biol Reprod, 80(2):367-74, Feb. 2009.
- Moalli PA, Debes KM, Meyn LA, Howden NS, & Abramowitch SD. Hormones restore biomechanical properties of the vagina and supportive tissues after surgical menopause in young rats. Am J Obstet Gynecol, 199(2):161e1-8, Aug. 2008.
- Alperin M, Debes K, Abramowitch S, Meyn L, & Moalli PA. LOXL1 deficiency negatively impacts the biomechanical properties of the mouse vagina and supportive tissues. Int Urogynecol J Pelvic Floor Dysfunct, 19(7):977-86, Jul. 2008.
- Moalli PA, Papas N, Menefee S, Albo M, Meyn L, & Abramowitch SD. Tensile properties of five commonly used mid-urethral slings relative to the TVT. Int Urogynecol J Pelvic Floor Dysfunct,19(5):655-63, May 2008.
- Zong W, Zyczynski HM, Meyn LA, Gordy SC, & Moalli PA. Regulation of MMP-1 by sex steroid hormones in fibroblasts derived from the female pelvic floor. Am J Obstet Gynecol, 196(4):349, Apr. 2007.
- Lowder JL, Debes KM, Moon DK, Howden N, Abramowitch SD, & Moalli PA. Biomechanical adaptations of the rat vagina and supportive tissues in pregnancy to accommodate delivery. Obstet Gynecol, 109(1):136-43, Jan. 2007.
- Daucher JA, Clark KA, Stolz DB, Meyn LA, & Moalli PA. Adaptations of the rat vagina in pregnancy to accommodate delivery. Obstet Gynecol, 109(1):128-35, Jan. 2007.
- Moalli PA, Klingensmith WL, & Meyn LA. Increased expression of matrix metalloproteinases in the uterine cervix of postmenopausal women. J Low Genit Tract Dis, 7(1):36-43, Jan. 2003.
- Alperin M & Moalli PA. Remodeling of vaginal connective tissue in patients with prolapse. Curr Opin Obstet Gynecol, 18(5):544-50, Oct. 2006.
- Moalli PA, Shand SH, Zyczynski HM, Gordy SC, & Meyn LA. Remodeling of vaginal connective tissue in patients with prolapse. Obstet Gynecol, 106(5 Pt 1):953-63, Nov. 2005.
- Moalli PA, Howden NS, Lowder JL, Navarro J, Debes KM, Abramowitch SD, & Woo SL. A rat model to study the structural properties of the vagina and its supportive tissues. Am J Obstet Gynecol, 192(1):80-8, Jan. 2005.
- Moalli PA, Klingensmith WL, Meyn LA, & Zyczynski HM. Regulation of matrix metalloproteinase expression by estrogen in fibroblasts that are derived from the pelvic floor. Am J Obstet Gynecol, 187(1):72-9, Jul. 2002.