Director
Timothy M. Crombleholme, MD, FACS, FAAP
Title
Director, Fetal Care Center of Cincinnati; Director, Center for Molecular Fetal Therapy
Appointment
Professor of Surgery, Obstetrics and Gynecology and Pediatrics (Molecular and Developmental Biology), University of Cincinnati College of Medicine
Bio
Timothy Crombleholme, MD, is a recognized leader in the field of fetal surgery and pediatric surgery. He comes to Cincinnati Children's Hospital Medical Center from the Center for Fetal Diagnosis and Treatment at Children's Hospital of Philadelphia (1996 to 2004). Previously he was director of the Fetal Treatment Program at the New England Medical Center in Boston, MA (1993 to 1995).
A graduate of Tufts University School of Medicine, Boston (1984), Dr. Crombleholme was a surgical resident and chief resident at the University of California at San Francisco (1984 to 1991), and a chief resident in pediatric surgery at The Floating Hospital for Infants and Children at the Tufts-New England Medical Center in Boston, MA (1991 to 1993). He trained under Michael Harrison, MD, who is widely recognized as the founder of fetal surgery.
In addition to his surgical expertise, Dr. Crombleholme is active in clinical and laboratory research. He established the Center for Molecular Fetal Therapy as the basic research laboratory component of the Fetal Care Center of Cincinnati.
Dr. Crombleholme's current clinical investigations include a National Institutes of Health funded multicenter trial to determine the best treatment for twin-twin tranfusion syndrome and research on new techniques for open fetal surgery and fetoscopic surgery. His laboratory research includes NIH-funded studies of gene therapy in tissue repair, fetal gene therapy and the role of the fetal fibroblast in fetal wound healing.
Credentials
BA: University of Pennsylvania, College of Arts and Sciences, Philadelphia, PA, 1980.
MD: Tufts University School of Medicine, Boston, MA, 1984.
Certification:
- Diplomate of the National Board of Medical Examiners, 1984.
- Diplomate of the American Board of Surgery, 1992.
- Special Qualification in Pediatric Surgery, 1994.
Awards and Honors
- Best Doctors in America, 2005, 2008
- Awarded "2005 Best Doctors"
- Awarded "2004 Best Doctors"
- Alpha Omega Alpha Honor Medical Society, 1984
- George L. Howland Prize, Tufts University School of Medicine, 1984
- Martin J. Loeb Prize, Tufts University School of Medicine, 1984
- Howard C. Naffziger Surgical Research Award, 1987
- AP Giannini Foundation Research Award, 1988
- J Engelbert Dunphy Research Competition Prize, University of California, San Francisco, 1988
- Young Investigator Award, American Society of Clinical Oncology, 1989
- Young Investigator Award, Surgical Section of the American Academy of Pediatrics, 1989
- American College of Surgeons Faculty Research Scholarship, 1995 to 1998
- Ethel Brown Foerderer Fellow, 1998 to 1999
- Career Development Award, American Diabetes Foundation, 1999
- Who's Who in Science and Engineering, 2000 to 2001
- Who's Who in Medicine, 2000 to 2001
- Who's Who in Diabetes Treatment, Education and Research, 2001
- Best Doctors in America, 2001 to 2004
Research
- Gene Therapy in Tissue Repair: The focus of this work is using adenoviral-mediated gene transfer to accelerate healing, prevent scar formation, or induce angiogenesis in a db / db diabetic mouse model.
- Fetal Gene Therapy: Using an in vitro model of fetal tracheal organ culture to assay efficiency of gene transfer and toxicity of various viral vectors including Ad, AAV, HSV, hybrid vectors, pseudotyped lentiviral vectors, application of sustained release vectors from hydrogels for fetal gene therapy in the tubes for cystic fibrosis in fetal lamb model, human-SCID mouse xenograft model.
- Role of the Fetal Fibroblast in Fetal Wound Healing: The focus of this work is the role of the fetal fibroblast in permitting scarless regenerative healing to proceed. Among numerous ongoing projects are studies on the cytokine response of the fetal fibroblast to wounding; the production of IL-8, IL-6, IL-10 by fetal fibroblasts; hyaluronic acid induction of cytokine expression in fetal macrophages; the role of hair follicle bulge cells in transitional fetal wound healing; HA receptor expression in fetal wounds; differential gene expression in fetal vs. adult fibroblasts.
- Fetal Gene Therapy in lamb and mouse models of GM1 gangliosidosis: Using ultrasound guided intra-ventricular injection of pig astrocytes retrovirally transfected in vitro with the LacZ reporter gene, we are attempting to develop a model of in-utero microglial transplantation for storage diseases. Transplanting prior to the development of immunocompetence, we have established microglial chimerism as an initial step in the development of packaging cell line to treat GM1 gangliosidosis in utero. Also, we have mouse model of GM1 gangliosidosis, which we are attempting to correct in utero using lentiviral vectors.
- Fetoscopic Surgery: The projects are focused on the development of new techniques to treat fetal diseases, including amniotic band syndrome and fetoscopic guided gene therapy.
- Fetal Tracheal Occlusion: The focus of this work is on the development of new minimally invasive techniques to achieve tracheal occlusion in diaphragmatic hernia. In addition, we have developed a human fetal trachea-SCID mouse xenograft model of tracheal occlusion to elucidate biologic mechanisms by which increased intratracheal pressure.
Research Grants and Contracts
Dermal-Epidermal Interactions in Diabetic Impaired Wound Healing, National Institutes of Health NIDDK, 9/30/00 to 8/31/05.
Twin-Twin Transfusion Syndrome Trial, National Institutes of Health, 7/1/01 to 6/30/06.
Publications, Most Recent
Connect to Timothy Crombleholme's publication on PubMed
Bouchard S, Johnson MP, Flake AW, Howell LJ, Myers LB, Adzick NS, Crombleholme TM. The EXIT procedure: Experience and outcome in 31 cases.J Pediaric Surgery, 37 (3) 418-426, 2002.
Crombleholme TM, Coleman B, Hedrick H, Liechty K, Howell L, Flake AW, Johnson M, Adzick NS. Cystic adenomatoid malformation volume ratio predicts outcome in prenatally diagnosed cystic adenomatoid malformation of the lung. J Pediatr Surg, 37 (3) 331-338, 2002.
Books, Most Recent:
Bianchi DW, Crombleholme TM, D'Alton ME, Fetology: Diagnosis and Management of the Fetal Patient, McGraw Hill, New York, NY, 2000. Awarded best textbook published in clinical medicine in 2000 by the Association of American Publishers.
Special Interests
