Kirsten Limesand, PhD

EDUCATION & PROFESSIONAL TRAINING

• Post-Doctoral, Signal Transduction, University of Colorado
• Ph.D., Virology, Colorado State University
• B.S., Microbiology, North Dakota State University

ACADEMIC ACTIVITIES

• Chair, Graduate Program Executive Committee
• Graduate Curriculum Subcommittee
• NSC 531 - Nutrition & Cancer (Offered Spring semester, odd years) - Course Syllabus
• NSC 308 - Nutrition and Metabolism - Course Syllabus

Public Relevance Statement:

Can you imagine having a mouthful of canker sores and cavities? Thousands of head and neck cancer patients suffer these consequences from radiation treatment. The Limesand lab works to prevent these side effects thereby improving patients' quality of life.

Clinical Relevance:
Radiation therapy for head and neck cancer causes adverse secondary side effects in the normal salivary gland including xerostomia, oral mucositis, malnutrition, and increase oral infections. Although improvements have been made in targeting radiation treatment to the tumor, the salivary glands are often in close proximity to the treatment site. The significant destruction of the oral cavity following radiation therapy results in diminished quality of life and in some cases interruptions in cancer treatment schedules.

RESEARCH & INTERESTS:
My research program has its foundation in radiation-induced gland dysfunction; mechanisms of damage, clinical prevention measures, and restoration therapies. Evidence suggests that salivary acinar function is compromised due to apoptosis induced by these treatments and temporary suppression of apoptotic events in salivary glands would have significant benefits to oral health. We utilize a number of techniques in my laboratory including: genetically engineered mouse models, real-time RT/PCR, immunoblotting, immunohistochemistry, primary cultures, siRNA transfections, irradiation, and procedures to quantitate salivary gland physiology.

Current Project Areas:

1. Radiation-induced apoptosis
2. Mechanisms of preserving salivary gland function
3. Identifying the radiosensitivity of salivary gland progenitor cells
4. Restoration of salivary gland function
5. Role of autophagy in radiation-induced loss of function

Involvement in Graduate Programs

• Nutritional Sciences (http://nutrition.cals.arizona.edu/graduate-degrees)
• Physiological Sciences (http://physiosc.web.arizona.edu/)
• Cancer Biology (http://www.azcc.arizona.edu/academics/cbio)

Please e-mail if interested in rotation or post-doctoral training opportunities.

University of Arizona Affiliations:

BIO5 Institute for Collaborative Research, University of Arizona Cancer Center

Peer-reviewed Publications

Limesand Lab:

• Avila JL, O Grundmann, R Burd and KH Limesand (2009). Radiation-induced salivary gland dysfunction results from p53-dependent apoptosis. International Journal of Radiation Oncology, Biology, Physics, 73(2):523-9.
• Grundmann O, GC Mitchell and KH Limesand (2009). Sensitivity of salivary glands to radiation: From animal models to therapies. Journal of Dental Research, 88(10):894-903.
• Limesand KH, S Said and SM Anderson (2009). Suppression of radiation-induced salivary gland dysfunction by IGF1. PLoS One, 4(3):e4663.
• Limesand KH, JL Avila, K Victory, H-H Chang, YJ Shin, O Grundmann and RR Klein (2010). IGF1 preserves salivary gland function following fractionated radiation, International Journal of Radiation Oncology, Biology, Physics, 78(2):579-86.
• Mitchell GC, JL Fillinger, S Sittadjody, JL Avila, R Burd and KH Limesand (2010). IGF1 activates cell cycle arrest following irradiation by reducing binding of ΔNp63 to the p21 promoter. Cell Death and Disease, 1:e50; doi:10.1038/cddis.2010.28.
• Vissink A, JB Mitchell, BJ Baum, KH Limesand, SB Jensen, PC Fox, LS Elting, JA Langendijk, RP Coppes and ME Reyland (2010). Clinical management of salivary gland hypofunction and xerostomia in head and neck cancer patients: Successes and barriers. International Journal of Radiation Oncology, Biology, Physics, 78(4):983-91.
• Grundmann O, JL Fillinger, KR Victory, R Burd and KH Limesand (2010). Restoration of radiation therapy-induced salivary gland dysfunction in mice by post therapy IGF1 administration. BMC Cancer, 10(1):417.
• Victory KR, R Burd, A Fribley, S Sittadjody, D Arnett, RR Klein and KH Limesand (2011). Tumor cell radiation response occurs in the presence of IGF1. Journal of Dental Research, 90(3):347-52.
• Jensen, SB, A Vissink, KH Limesand and ME Reyland (2011). Salivary gland hypofunction and xerostomia in head and neck radiation patients. Invited review to JNCI Monograph.
• Bathke, MM, K Martin and KH Limesand (2012). Salivary Glands and Saliva, Encyclopedia of Human Biology, 3rd Edition, M. Watsky, ed., Elsevier.
• Martin KL, RR Klein, DG Arnett, R Burd and KH Limesand (2012). Prevention of Radiation-Induced Salivary Gland Dysfunction Utilizing a CDK Inhibitor, PLoS One, 7(12): e51363
• KH Limesand, AM Chibly, and A Fribley (2013). Impact of targeting insulin-like growth factor signaling in head and neck cancers. Growth Hormone and IGF Research, Oct;23(5):135-40.
• Morgan-Bathke, M, H Lui, G Hill, Chibly, AM, DK Ann and KH Limesand (2013). Salivary phenotype of mice with impaired autophagy (Atg5f/f;Aqp5-Cre), Journal of Dental Research, Oct;92(10):911-7
• Morgan-Bathke, M, GA Hill, ZI Harris, HH Lin, AM Chibly, RR Klein, R Burd, DK Ann and KH Limesand (2014). Autophagy Correlates with Maintenance of Salivary Gland Function Following Radiation. Scientific Reports, 4:5206.
• Chibly, AM, L Querin, ZI Harris and KH Limesand (2014). Label-Retaining Cells in the Adult Murine Salivary Glands Possess Characteristics of Adult Progenitor Cells. PLoS One, 9(9):e107893.
• Chibly, AM, T Nguyen and KH Limesand (2014). Palliative Care for Salivary Gland Dysfunction Highlights the Need for Regenerative Therapies. A Review on Radiation and Salivary Gland Stem Cells. Journal of Palliative Care & Medicine, accepted
• Lin HH, S Lin, Y Chung, S Vonderfecht, JM Camden, P Flodby, Z Borok, KH Limesand, N Mizushima and DK Ann (2014). Autophagy modulates acute and subacute duct ligation-induced inflammation, senescence and apoptosis in mouse submandibular glands. Cell Death and Disease, accepted.
• Hill, GA, D Headon, ZI Harris, K Huttner and KH Limesand (2014). Pharmacological Activation of the EDA/EDAR Signaling Pathway Restores Salivary Gland Function Following Radiation-Induced Damage, PLoS One, accepted.
• Morgan-Bathke, M, ZI Harris, Arnett D, RR Klein, R Burd, DK Ann and KH Limesand (2014). The Rapalogue, CCI-779, Improves Salivary Gland Function Following Radiation. PLoS One, accepted

Collaborations

• Thangasamy T, S Sittadjody, GC Mitchell, EE Mendoza, VM Radhakrishnan, KH Limesand and R Burd (2009). Quercetin abrogates chemoresistance in melanoma cells by modulating deltaNp73. BMC Cancer, 10(1):282.
• Thangasamy T, S Sittadjody,GC Mitchell, EE Mendoza, VM Radhakrishnan, KH Limesand and R Burd (2010). Exploiting tyrosinase expression and activity in melanocytic tumors: Quercetin and the central role of p53. Integrative Cancer Therapies.
• Mendoza EE, MG Pocceschi, X Kong, DB Leeper, J Caro, KH Limesand, and R Burd (2012). Control of Glycolytic Flux by AMPK in Tumor Cells Adapted to Low pH. Translational Oncology
• Kusne, Y, E Goldberg, SS Parker, SM Hapak, I Maskaykina, WM Chew, KH Limesand, HL Brooks, TJ Price, N Sanai, J Nikolich-Zugich, and S Ghosh (2013). Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice, Age 36(1):199-212
• Goldberg, EL, J Romero-Aleshire, KR Renkema, MS Ventevogel, WM Chew, JL Uhrlaub, MJ Smithey, KH Limesand, GD Sempowski, HL Brooks and J Nikolich-Zugich (2014). Lifespan-extending caloric restriction or mTOR inhibition impairs adaptive immunity of old mice by distinct mechanisms. Aging Cell, accepted.