Regina Day Ph.D.

Education

A.B. Smith College, Northampton, MA, USA
Ph.D. Tufts University, Boston, MA, USA

Biography

Introduction and overview:
My laboratory is dedicated to understanding normal tissue repair processes and how the repair process is altered in fibrotic remodeling. Normal tissue regeneration for wound healing is a critical focus of research for the military as well as for the medical field in general. The long term goal of my laboratory is to understand the mechanisms of repair failure and fibrotic repair and to identify therapeutic agents to prevent and/or treat this disease. The hematopoietic system is a model of repair failure after total body irradiation, and allows for the investigation of the response of stem and progenitor cells to radiation damage. The lung provides an excellent model system for investigation of fibrotic repair, since it is uniquely sensitive to radiation, producing well-defined stages of injury, inflammation, attempted repair, and repair failure/remodeling. Lung fibrosis is a progressive disease with no treatments and poor prognosis. Our laboratory uses in vivo animal models and in vitro primary cell cultures to systematically elucidate the mechanisms of tissue regeneration and fibrotic remodeling at the molecular, biochemical, cellular, and tissue levels.

Radiation countermeasures for the lung and hematopoietic systems and radiation biology:
• Radiation countermeasures for both the hematopoietic and lung tissues. Radiation-induced lung injury is a late effect of radiation, whereas hematopoietic injuries are an acute radiation injury. Because of the Department of Defense’s interest in protection against both acute and delayed injuries, we were requested to develop a murine model for both the hematopoietic and pulmonary injuries, and to test radiation countermeasures in both systems. My laboratory developed an animal model system incorporating both hematopoietic and lung radiation injuries. We have determined the mechanism of action of captopril protection in both tissues, as a part of the requirement for radiation countermeasure development under the Animal Rule for the FDA. We are currently expanding our testing of captopril in the minipig model of radiation acute injuries.
• My laboratory developed a cell culture system for studying the molecular mechanisms of radiation-induced senescence in normal (non-transformed, non-immortalized) cells. Our research demonstrated for the first time that normal lung and skin cells primarily undergo accelerated senescence, and not apoptosis, in response to radiation. We identified an early cellular response to radiation is the induction of insulin-like growth factor 1 (IGF-1) and the activation of its receptor (IGF-1R). These novel and provocative observations prompted us to hypothesize that senescence is the precipitating state for radiation pathology.

Hepatocyte growth factor (HGF) signaling for tissue repair and suppression of fibrosis:
• My laboratory has identified novel signaling pathways for HGF-induced normal tissue repair mechanisms. HGF expression is required for normal tissue repair, and HGF can redirect repair away from fibrotic remodeling to induce normal tissue regrowth. To understand how HGF can accomplish this, my research team investigated signal transduction mechanisms for HGF suppression of apoptosis in epithelial and endothelial cells that is induced during fibrosis. We next investigated the mechanisms by which HGF expression is suppressed during fibrotic remodeling. We recently uncovered a novel mechanism by which miRNA regulates HGF mRNA half-life under fibrotic conditions. This research led to the identification of potential novel anti-fibrotic treatment strategies.
• My laboratory developed a synthetic peptide based on other proteins that bind the HGF receptor, MET. The structural complexity of the full length HGF structure has prevented its development as a pharmaceutical agent, and full length HGF has not been successfully produced in sufficient quantities for clinical use. A patent was submitted by the USU/HJF JOTT based on these findings. Our laboratory currently aims to improve the design of this protein, to improve stability and increase receptor affinity.

Career Highlights: Positions, Projects, Deployements, Awards and Additional Publications

12/2016 – present Vice Chair USUHS School of Medicine Department of Pharmacology and Molecular Therapeutics

7/2014- present Professor USUHS School of Medicine Primary Appointment Department of Pharmacology

11/2014 Adjunct Professor Georgetown University School of Medicine Pulmonary, Critical Care, and Sleep Medicine

2/2010- 7/2014 Associate Professor USUHS School of Medicine Primary Appointment Department of Pharmacology

7/2004-1/2010 Tenure Track Assistant Professor USUHS School of Medicine Primary Appointment Department of Pharmacology

1/2004-6/2004 Research Assistant Professor Georgetown Univ. School of Medicine Pulmonary, Critical Care, and Sleep Medicine

8/1999-12/2004 Research Assistant Professor Tufts-New England Medical Ctr Pulmonary, Critical Care, and Sleep Medicine Div

Postdoctoral Fellow NIH, NCI, Lab of Cellular, Molecular Biology

Representative Bibliography

Landauer, M.R., Harvey, A.J., Kaytor, M.D., Day, R.M. (2019) Mechanism and therapeutic window of a genistein nanosuspension to protect against hematopoietic-acute radiation syndrome. J. Radiat. Res. In press.

McCart, E.A., Lee, Y.H., Jha, J., Mungunsukh, O., Rittase, W.B., Summers, T.A., Muir, J., Day R.M. (2019) Delayed captopril administration mitigates hematopoietic injury in a murine model of total body irradiation. Sci Reports, 9: 2198.

75. Rittase, W.B., McCart, E.A., Muir, J.M., Bouten, R.M., Slaven, J.E., Bylicky, M.A., Wilkins, W.L., Lee, S-H., Gudmundsson, K.O., Di Pucchio, T., Olsen, C.H., Du, Y., Day, R.M. (2021) Effects of captopril against radiation injuries in the Gottingen minipig model of hematopoietic-acute radiation syndrome. PLoS One, 16:e0256208.

Corey, S.J., Jha, J., McCart, E.A., Rittase, W.B., George, J., Mattapallil, J.J., Mehta, H., Ognoon, M., Bylicky, M.A., Summers, T.A., Day, R.M. (2018) Captopril mitigates splenomegaly and myelofibrosis in the Gata1low murine model of myelofibrosis. J Cell Mol Med, 22: 4274-4282.

Du, Y., Banas, R.A., McCart, E.A., George, J., Oakley, K., Han, Y., Landauer, M.R., Day, R.M. (2018) Effect of human amnion-derived multipotent progenitor cells on hematopoietic recovery after total body irradiation in C57BL/6 mice. Int J Radiat Res, 16:155-168.

Zhao*, J., Day*, R.M., Jin, J-Y., Quint, L., Williams, H., Ferguson, C., Yan, L., King, M., Albsheer, A., Matuszak, M., Kong, S-M. (2017) Thoracic radiation-induced pleural effusion and risk factors in patients with lung cancer. Oncotarget, 8: 97623-32.

McCart, E.A., Lombardini, E., Mog, S.R., Panganiban, R.A.M., Dickson, K.M., Mansur, R.A., Nagy, V., Kim, S-Y., Selwyn, R., Landauer, M.R., Darling, T.N., Day, R.M. (2017) Accelerated senescence in a murine model of radiation-induced skin injury. J Radiat Res, 58: 636-646.

77. Rittase, W.B., Slaven, J.E., Suzuki, Y.J., Muir, J.M., Lee, S-H., Rusnak, M., Brehm, G.V., Bradfield, D.T., Symes, A., Day, R.M. (2022) Iron Deposition and Apoptosis/Ferroptosis in the Spleen in a Murine Model of Acute Radiation Syndrome. IJMS. 23:11029.

Barshishat-Kupper, M., McCart E.A., Freedy, J.G., Tipton A.J., Nagy V., Kim, S.-Y., Landauer, M.R., Mueller G.P., Day R.M. (2015) Protein oxidation in the lungs of C57BL/6J mice following X-irradiation. Proteomes, 3, 249-265.

78. Slaven, J.E., Wilkerson, M., Soltis, A.R., Rittase, W.B., Bradfield, D.T., Bylicky, M., Cary, L., Tsioplaya, A., Bouten, R., Dalgard, C.L., Day, R.M. (2023) Transcriptomic profiling and pathway analysis of mesenchymal stem cells following low dose-rate radiation exposure. Antioxidants. 12:241.