As a graduate and post-doctoral fellow, I worked exclusively with Drosophila focusing on Hox gene biology and cell signaling in fly development. An interest in pursuing translational research led me to accept a position as a Project Scientist at the Cleveland Clinic Florida to study the role of the transcription factor Hoxb13 in cutaneous wound healing using a Hoxb13 knock out (KO) mouse line. I have found that Hoxb13 KO unwounded skin exhibits higher levels of hyaluronan (HA) and reduced expression of epidermal differentiation markers compared to wild-type (WT) mice, and that Hoxb13 KO wounds exhibit enhanced wound healing compared to WT mice. Together, these results indicate that Hoxb13 functions in the everyday epidermal differentiation program and in cutaneous wound repair. The continued study of Hoxb13 in skin is important because several skin diseases are associated with differentiation defects and poor wound healing is a major health concern. My previous training and current environment are not sufficient to carry this investigation further. Therefore, I will be transferring to the Lerner Research Institute's Department of Biomedical Engineering at the Cleveland Clinic Foundation in Ohio, effective June 1, 2003 where I will be under the direction of Vincent Hascall, Ph.D., a leading expert in HA biology and Edward Maytin, M.D. Ph.D., a dermatologist with extensive scientific experience in the molecular biology of skin development and disease. My immediate goals are 1) to confirm a role for Hoxb13 in promoting epidermal differentiation, 2) to determine if Hoxb13 directly regulates the expression of HA metabolic genes, and 3) to evaluate the effects of altered Hoxbl 3 expression in in vitro wound healing models. My research career development plan will encompass learning the research skills necessary to meet these goals including 1) the use of an organotypic keratinocyte system to study the effects of altered Hoxb13 expression, promoter analyses, and in vitro wound healing assays. I will also give yearly seminars, receive yearly progress evaluations, and attend a formal seminar series on skin biology and disease. My long-term goals are 1) to understand how Hox genes coordinately function in skin renewal and repair, 2) to identify direct targets of Hox transcriptional activity in skin, and 3) to identify particular Hox genes as potential clinical targets in the case of skin disease and/or inadequate wound healing.
|Mack, Judith A; Maytin, Edward V (2010) Persistent inflammation and angiogenesis during wound healing in K14-directed Hoxb13 transgenic mice. J Invest Dermatol 130:856-65|
|Mack, Judith A; Anand, Sanjay; Maytin, Edward V (2005) Proliferation and cornification during development of the mammalian epidermis. Birth Defects Res C Embryo Today 75:314-29|
|Mack, Judith A; Li, Ling; Sato, Nobuyuki et al. (2005) Hoxb13 up-regulates transglutaminase activity and drives terminal differentiation in an epidermal organotypic model. J Biol Chem 280:29904-11|