February 28, 2020

The Basic Science of Uterine Fibroids Scientific Meeting – February 28, 2020

On Friday, February 28, 2020, we are sponsoring a scientific meeting on the Basic Pathobiology of Uterine Fibroids to be held at NIEHS, Research Triangle Park, NC. Presentations from scientists working on the basic mechanisms of fibroid development and growth, as well as new therapeutic approaches will be featured. The program committee members are Donna Baird, PhD, NIEHS, James Segars, MD, Johns Hopkins Medical School, Phyllis Leppert, MD, PhD, Duke University, Friederike Jayes, DVM, PhD, Duke University, and Quaker Harmon, PhD, NIEHS

February 28, 2020
NIEHS, Research Triangle Park, NC

Please mark your calendars and plan to attend. Abstracts are encouraged. The planning committee will choose three submitted abstracts for oral presentation. Those chosen for oral and poster presentation will be notified by February 8th, 2020. Please submit an 350 word abstract by February 1, 2020 to  

Please visit the NIEHS site for parking and navigation information. Ride sharing using Uber has more success navigating the NIEHS campus. Direct all ride-share drivers to use the T.W. Alexander NIEHS gate only, Do NOT use any Hopson Road Gates nor the EPA Gate on T.W. Alexander Drive. Arrive at least ½ hour early to get through security.

Register

February 29, 2020
Gala Dinner Dance
Please save Saturday, February 29, 2020 for a Gala Dinner Dance at the Croasdaile Country Club, Durham, NC. We plan to have a Leap Day Party in honor of our fifth Gala in North Carolina.

Register

Schedule

  • 8:00AM: Light Breakfast
  • 8:30AM: Plenary speaker: Serdar Bulun, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Ill. Current knowledge of the molecular biology of uterine fibroid: the whole spectrum
  • 9:00 AM: Featured Speaker: Daniel J. Tschumperlin, Division of Physiology and Biomechanical Engineering, Mayo Clinic, Rochester, MN; Mechanosensing and fibrosis
  • 9:30 AM: Coffee break
  • 10:00 AM: Current research contributions to understanding uterine fibroid biology:
    • Jose Teixeria, Michigan State University, Signaling mechanisms of Wnt/β catenin in fibroids, activation and epigenetics
    • Darlene Dixon, NIEHS, RTP, NC, The Life Cycle of the Uterine Monocyte
    • Ami Zota, George Washington University, Washington, DC, Phthalates exposure and uterine fibroid burden among women undergoing surgical treatment
    • Bill Catherino, USUHS, Bethesda, MD, The role of AP-1 in collagen deposition in uterine fibroids.
    • Saiji Ahonen, University of Helsinki, Helsinki, Finland, MED12 mutations and fibroids, clinical correlatons
    • Carlos Simon, Harvard University, Boston, MA, Single cell RNAseq provides a molecular and cellular cartography of the human myometrium and uterine fibroids
  • 11:00 AM: Discussion, Q and A for Speakers
  • 11:30: Lunch. On own in the NIEHS cafeteria.
  • 12:30: Poster Session
  • 1:30PM: New and young investigators: Oral Presentations of ten minutes each chosen from the abstracts submitted.
  • 2:30PM: Short Break
  • 2:45PM: Lessons learned in the understanding of uterine fibroid biology from treatment approaches and developmental exposures.
    • Elizabeth Stewart, Mayo Clinic, Rochester, MN: What clinical trials and treatment approaches tell us about uterine fibroid biology.
    • Andrea Tinelli, Vito Fuzzi Hospital, Lecce, Italy: Biology and histology of the pseudocapsule.
    • Ayman Al Hendy, University of Illinois, Chicago, Ill: Vitamin D, green tea extract and other nutritional treatment approaches: What we have learned.
    • Friederike Jayes, Duke University, Durham, NC: Heterogeneity of interstitial collagen and stiffness in uterine fibroids.
    • Jim Segars, Johns Hopkins, Baltimore, MD: Molecular mechanisms of action of Clostridia Histolyticum collagenase on fibroid cells as well as interstitial collagen.
    • Mark Palmeri, Duke University, Durham, NC: Shear Wave Elasticity Imaging to Characterize Cervical Compliance and Soft Tissue Tumors ( implications for imaging of fibroids).
  • 3:45PM: Discussion, Q and A for Panel
  • 4:15PM: Short Coffee Break
  • 4:30PM: Where do we go from here: Questions to be studied in future research: Is there a unifying story?
    Jim Segars, Donna Baird, Friederike Jayes, Phyllis Leppert
  • 5:00PM: Adjourn

Planning committee questions for Discussion

  • What can we learn about the presence of neuropeptides and neurotransmitter activity in the pseudocapsule, what if any are the impact of hormones on the origin and growth of neurotransmitters in the pseudocapsule? How do they impact on the symptoms of pain?
  • What is unique about the myometrium and the uterine smooth muscle cells compared to the smooth muscle of heart, blood vessels and the GI tract? They are subject to compression and stretch so I image that these are also subjected to mechanotransduction as well as chemical signaling – The uterus has the capacity to develop many more leiomyomas than these tissues.
  • MED-12 mutations are found in other disease states- prostate cancer is one – what is the trigger or contributing factors for these mutations? MED-12 is in a complex of 26 subunits and this complex is extremely dynamic. Those who study the whole complex do not agree completely on its physical chemistry and its stoichiometry. How does the MED-12 mutation change the signaling at a molecular level? The MED-12 complex is considered to be the final molecule of a signaling cascade as it is the molecule that functions in transcription and thus alters the gene expression and thus ultimately cell behavior. What do we know about the epigenetics in terms of MED-12? What is the role of the high mobility genes that are found in those tumors that do not have MED-12 mutations?
  • Why do more fibroids form in the uterine fundus than in other areas?
  • What are the mechanisms that prevent fibroids in the women who do not get them? Is it really 25% of women?
  • What is the role of mechanotransduction in the initiation of fibroids? There is microscopic evidence of increased collagen in seedling fibroids. While ECM accumulates as fibroids grow, the fact that the ECM surrounding only one cell is most likely stiffer than the adjacent myometrium would cause some altered signaling. In other tissues MT has been documented to alter gene expression as the MT forces also affect the nucleus. Cell injury causes changes in fluid dynamics which impacts on stiffness on the cell. How does this alter signaling in early fibroid initiation?
  • Does menstrual blood which extravasates into the myometrium cause an injury that begins the process of initiation of fibroids?
  • What does CHC (collagenase from bacteria due to cells? Are they altered?
  • What is the origin of uterine stem cells, are they really resident cells or are then fibrocytes? The biomarkers of these cells are very similar to those of stem cells. 
  • Finally, how can we determine prior to treatment if a tumor is a fibroid, (leiomyoma} or a leiomyoscarcoma?
  • Where do the myometrial stem cells come from (resident from birth? Migrated from? reversion of resident myometrial cells to pluripotent state?
  • What factors increase mutation rates that lead to more transformed fibroid stem cells?
  • What is required for a transformed cell to proliferate into a detectable fibroid?
  • What is the prevalence of MED12 mutation in newly developed fibroids (look at those ≤1cm in diameter in relatively young women)?
  • Does anemia increase risk of fibroid development (increased angiogenesis)
  • What stimulated the immune response in fibroid lesion that triggers fibrosis?
  • What factors increase fibroid growth and are they different for MED12 tumors than for other types?
  • Are the different types of fibroids (regular, cellular, those with lipid invasion) different in genetics?
  • Other than location and size, are some fibroids more likely to cause symptoms than others?
  • What type (s) of fibroids do not respond (shrink) with Ulipristal Acetate treatment?