Page 51 - Hormel Report 2021

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Current research projects:
1. Identification of novel epidermal progenitors The major goals of this project are to deter- mine the stem cell properties of bone marrow- and blood- derived epithelial cells by placing them into our in vitro and in vivo assays for epidermal stem cells.
2. The Hormel Institute’s Windfeldt Cancer Research Award
A novel model for distinguishing low- and high-risk benign papillomas induced by solar ultraviolet radiation
3. Testing the epithelial transit hypothesis
The major goal of this project is to define reciprocal interactions between epithelial cells of the epidermis and the bone marrow.
Publications:
• Trempus, C.S., Morris, R.J., Bortner, C.D., Faircloth, R.S., Reece, J.M., and Tennant, R.W. Enrichment for living murine keratinocytes from the hair follicle bulge with the cell surface marker CD34. J. Invest. Dermatol 2003, 120: 501-511, *CST and RJM contributed equally as first author of this work. [PMID: 12648211]
• Morris, R.J., Liu, Y., Marles, L., Yang, A., Trempus, C., Li, S., Lin, J.S., Sawicki, J.A., and Cotsarelis, G. Capturing and profiling adult hair follicle stem cells, Nat Biotechnol. 2004, April;22 (4): 411-417. (*RJM and GC share equally as senior author). [PMID: 15024388]
• Park H., Lad, S., Boland, K, Johnson, K., Readio, N., Jin, Guangchun , Asfaha, S., Patterson,
K.S., Singh, A., Yang, X., Londono, D., Singh,
A., Trempus, C., Gordon, D., Wang, T.C., and Morris, R.J. Bone marrow-derived epithelial cells and hair follicle stem cells contribute to development of chronic cutaneous neoplasms. Nat Commun. 2018 Dec 13;9(1):5293. doi: 10.1038/s41467-018-07688-8. PubMed
PMID: 30546048; PubMed Central PMCID: PMC6294255.
recruited to chronically compromised epithelium and regenerate it. Our specific aims are to analyze these cells in vitro and in vivo using strategies that my laboratory and others have developed for identifying epithelial stem cells in hair follicles and epidermis. This research is highly significant and will contribute to understanding epithelial biology and hematology in general, to the validation of liquid biopsy as a diag- nostic tool in cancer research and help us to achieve our goal of preventing and curing chronic cutaneous diseases including cancer, psoriasis, and epidermol- ysis bullosa. The scientific premise supporting this hypothesis is predicated upon: 1) RT-PCR detection of traces of cytokeratin expression in blood and bone marrow of “normal, healthy human subjects;
2) similar literature reporting rare bone marrow derived epithelial cells recruited temporarily to the cutaneous epithelium upon acute injury; 3) sever- al high quality case reports; and 4) our own data demonstrating their recruitment to a subset of squamous papillomas; and our documenting the their presence in “normal” blood and bone marrow by four different methods.
In a second project, we combine immunofluores- cence microscopy with computer analysis with the goal of differentiating between high and low risk benign papilloma tumors. High risk papillomas are more likely to become carcinomas than those with low risk. Treatment for carcinoma varies by the
type of cancer and options include surgery, radia- tion therapy, chemotherapy, targeted therapy, and immunotherapy. Using computer analysis to aid in diagnosing the risk level of the papilloma would give both doctors and patients the opportunity to choose the appropriate time and type of treatment plan. This project aims to test the following hypothesis:
if the papilloma is high risk, it is likely that there will be more GFP-labeled cells in the dermis and epider- mis than if it were a low risk papilloma. This hypo- thesis will be tested by continued image production and analysis to look at ratios of GFP-labeled cells to total cells (DAPI), as well as location of the GFP- labeled cells. The project findings are being ana- lyzed, and differences between high and low risk papillomas are under investigation.