Research

Tumor microenvironment:

Withers SS, Moeller CE, Quick CN, Liu CC, Baham SM, et al. Effect of stimulator of interferon genes (STING) signaling on radiation-induced chemokine expression in human osteosarcoma cells. PLOS ONE. 2023; 18(4): e0284645.

Costa VR, Soileau AM, Liu CC, Moeller CE, Carossino M, Langohr IM, Withers SS. Exploring the association of intratumoral immune cell infiltrates with histopathologic grade in canine mast cell tumors. Research in Veterinary Science. 2022; 147:83-91.  

Targeted cancer therapeutics:

Singh SS, Mattheolabakis G, Gu X, Withers SS, Dahal A, Jois S. A grafted peptidomimetic for EGFR heterodimerization inhibition: Implications in NSCLC models. European Journal of Medicinal Chemistry. 2021; 216. 

Canine onco-immunology:

Soileau AM, Quick CN, Moeller CE, Schaumburg JC, Withers SS. The effect of arginase on canine T-lymphocyte functions and its modulation by all-trans retinoid acid (ATRA) in canine monocyte-derived macrophages. Veterinary Sciences. 2022; 9(7):374. 

Bauman AB, Moeller CE, Soileau AM, Goodermuth CE, Costa VR, Schaumburg JC, Pucheu-Haston CM, Welborn ND, Dehghanpir SD, Mitchell MA, Withers SS. Canine memory T-cell subsets in health and disease. Veterinary Immunology and Immunopathology. 2022; 246:110401.

Withers SS, Sparger EE, Boudreaux B, Mason NJ. Utilizing microbes to treat naturally occurring cancer in veterinary species. Current Clinical Microbiological Reports. 2019; 6, 200–212. 

Clinical veterinary oncology:

Moses, AA, Robinson, CJ, Rincon, AA, Wurlod, VA, Withers, SS. Autologous blood patch pleurodesis for management of persistent pneumothorax in a dog with metastatic osteosarcoma. Vet Rec Case Rep. 2023;e601. 

Groves PK, Liu CC, Geels OR, Withers SS. The use of "trend" statements in veterinary oncology literature. Veterinary and Comparative Oncology. 2022. 

Hu TG, Dehghanpir SD, Sasaki E, Costa VR, Pucheu-Haston CM, Del Piero F, Withers SS. Pathology in Practice. Journal of the American Veterinary Medical Association. 2022 May 11;259(S2):1-4. 

 

Previous work performed by Dr. Withers and others, at the University of California- Davis:

Tumor microenvironment:

Withers SS, York D, Choi JW, Woolard KD, Laufer-Amorim R, Sparger EE, Burton JH, McSorley SJ, Monjazeb AM, Murphy WJ, Canter RJ, Rebhun RB. Metastatic immune infiltrates correlate with those of the primary tumour in canine osteosarcoma. Vet Comp Oncol. 2019 Sep;17(3):242-252.

Withers SS, Skorupski KA, York D, Choi JW, Woolard KD, Laufer-Amorim R, Sparger EE, Rodriguez CO, McSorley SJ, Monjazeb AM, Murphy WJ, Canter RJ, Rebhun RB. Association of macrophage and lymphocyte infiltration with outcome in canine osteosarcoma. Veterinary and Comparative Oncology. 2019; 17(1): 49-60.

Targeted cancer therapeutics:

Wang Z, Aguilar EG, Luna JI, Dunai C, Khuat LT, Le CT, Mirsoian A, Minnar CM, Stoffel KM, Sturgill IR, Grossenbacher SK, Withers SS, Rebhun RB, Hartigan-O'Connor DJ, Méndez-Lagares G, Tarantal AF, Isseroff RR, Griffith TS, Schalper KA, Merleev A, Saha A, Maverakis E, Kelly K, Aljumaily R, Ibrahimi S, Mukherjee S, Machiorlatti M, Vesely SK, Longo DL, Blazar BR, Canter RJ, Murphy WJ, Monjazeb AM. Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nat Med. 2019 Jan;25(1):141-151.

Withers SS, York D, Johnson E, Al-Nadaf S, Skorupski KA, Rodriguez Jr. CO, Burton JH, Guerrero T, Sein K, Wittenburg L, Rebhun RB. In vitro and in vivo activity of liposome-encapsulated curcumin for naturally occurring canine cancers. Veterinary and Comparative Oncology. 2018; 16(4): 571-579.

York D, Withers SS, Watson KD, Seo KW, Rebhun RB. Enrofloxacin enhances the effects of chemotherapy in canine osteosarcoma cells with mutant and wild-type p53. Veterinary and Comparative Oncology. 2017; 15(3): 1087-1100.

Shahi MH, York D, Gandour-Edwards R, Withers SS, Holt R, Rebhun RB. BMI1 is expressed in canine osteosarcoma and contributes to cell growth and chemotherapy resistance. PLOS One. 2015; 
10(6): e0131006.

Canine onco-immunology:

Sparger EE, Chang H, Chin N, Rebhun RB, Withers SS, Kieu H, Canter RJ, Monjazeb AM, Kent MS. T cell immune profiles of blood and tumor in dogs diagnosed with malignant melanoma. Frontiers In Veterinary Science. 2021; 8. 

Choi JW, Withers SS, Chang H, Spanier JA, De La Trinidad VL, Panesar H, Fife BT, Sciammas R, Sparger EE, Moore PF, Kent MS, Rebhun RB, McSorley SJ. Development of canine PD-1/PD-L1 specific monoclonal antibodies and amplification of canine T cell function. PLoS One. 2020 Jul 2;15(7).

Withers SS, Chang H, Choi JW, McSorley SJ, Kent MS, Monjazeb AM, Murphy WJ, Moore PF, Sparger EE, Rebhun RB. Multicolor flow cytometry for evaluating age-related changes in memory lymphocyte subsets in dogs. Developmental and Comparative Oncology. 2018; 87: 64-74.

Park JS*, Withers SS*(equal effort with Park JS), Modiano JF, Kent MS, Chen M, Luna JI, Culp WTN, Sparger EE, Rebhun RB, Monjazeb AM, Canter RJ, Murphy WJ. Canine cancer immunotherapy studies: Linking mouse and human. J Immunotherapy Cancer. 2016; 4, 97.

Clinical veterinary oncology:

Rebhun RB, Kass PH, Kent MS, Watson KD, Withers SS, Culp WTN, King AM. Evaluation of optimal water fluoridation on the incidence and skeletal distribution of naturally arising osteosarcoma in pet dogs. Veterinary and Comparative Oncology. 2017; 15(2): 441-449.

Withers SS, Lawson CM, Burton AG, Rebhun RB, Steffey MA. Management of an invasive and metastatic Sertoli cell tumor with associated myelotoxicosis in a dog. Canadian Veterinary Journal. 2016; 57(3): 299-304.

Withers SS, Johnson EG, Culp WTN, Rodriguez Jr. CO, Skorupski KA, Rebhun RB. Paraneoplastic hypertrophic osteopathy in 30 dogs. Veterinary and Comparative Oncology. 2015; 13(3): 157-165.

Withers SS, Kass PH, Rodriguez Jr, CO, Skorupski KA, O’Brien D, Guerrero T, Sein K, Rebhun RB. Fasting reduces the incidence of delayed-type vomiting associated with doxorubicin treatment in client owned dogs with lymphoma. Translational Oncology. 2014; 7(3): 377-383.

Representative examples of immune cell infiltrates in low- and high-grade cutaneous canine mast cell tumors (ccMCT) determined by immunohistochemistry. T-lymphocyte infiltrates (CD3+) in a low- (A) and high-grade (B) ccMCT. T-regulatory cell infiltrates (FOXP3+) in a low- (C) and high-grade (D) ccMCT. Macrophage infiltrates (Iba1+) in a low- (E) and high-grade (F) ccMCT. PD-1+ cell infiltrates in a low- (G) and high-grade (H) ccMCT. 100x magnification (200 μm bar) with 400x insets (50 μm bar). Bar lengths are included for scale. Published in Research in Veterinary Science.

 

Granzyme B (GZMB) expression in canine CD8+ T-lymphocytes exposed to arginase. PBMCs from three dogs were incubated in complete media, with or without indicated concentrations of arginase (25–100 nM), for two days prior to flow cytometry analysis. CD8+ T-lymphocytes were analyzed after first gating on the lymphocyte cloud, single cells, live cells, CD3+, and CD4−CD8+ cells. Representative scatter plots (A) and summary graph (B) show the proportion of GZMB+ CD8+ T-lymphocytes with increasing concentrations of arginase. Lines connect data points from each individual dog. * p < 0.05; *** p< 0.001; n = 3. Published in Veterinary Sciences.

 

Association of macrophage tumor infiltration with outcome in canine osteosarcoma. Kaplan Meier curves summarizing the A) disease-free interval, and B) survival times of dogs with %CD204+ values above (grey line) or below (black line) the median. Tick marks represent censored events. P values are shown. Published in Veterinary and Comparative Oncology.

 

Alterations to T cell memory subset frequencies in fresh PBMCs of young vs. aged dogs. Representative flow cytometry scatter plots illustrating memory subset frequencies of CD4+ and CD8+ T cells in a young/lean dog and an aged/lean dog. CM = central memory; EM = effector memory; TEMRA = terminal effector memory CD45RA-expressing.

Frequencies of T cells with various memory phenotypes in young vs. aged dogs. Means and standard deviations are shown.  * P ≤ 0.05; ** P ≤ 0.01; n = 6 per age group. Published in Developmental and Comparative Immunology.

2022- Veterinary Cancer Society Meeting

Robinson C, Moeller C, Quick C, Goodermuth C, Carossino M, Withers S. Expression of macrophage-colony stimulating factor (M-CSF) and interleukin-34 (IL-34) expression in canine osteosarcoma (Poster Presentation). ***Awarded the Edward L. Gillette Memorial Award for Outstanding Poster- Research Project***

Christopher Robinson presenting his research at the 2022 Veterinary Cancer Society Meeting in Norfolk, VA.

2022- LSU Discover Day Symposium

Quick C, Moeller C, Fuselier J, Withers S. Expression of neonatal Fc receptor (FcRn) and cytotoxicity of albumin-ansamitocin P-3 in human and canine osteosarcoma cell lines (Poster Presentation)

2022- Phi Zeta Research Emphasis Day Virtual Meeting

Moeller C, Liu C, Quick C, Baham S, Subramanian R, Kousoulas K, Withers S. Effect of stimulator of interferon genes (STING) signaling on radiation-induced chemokine expression in human osteosarcoma cells (Poster Presentation)

Quick C, Moeller C, Fuselier J, Withers S. Expression of neonatal Fc receptor (FcRn) in human and canine osteosarcoma cells (Poster Presentation)

Robinson C, Moeller C, Quick C, Goodermuth C, Carossino M, Withers S. Modulation of M-CSF and IL-34 expression by canine osteosarcoma cells exposed to inflammation and chemotherapy (Poster Presentation)

Groves P, Liu CC, Geels O, Withers S. The use of “trend” statements in veterinary oncology literature (Poster Presentation)

Cally Quick presenting her research at the 2022 LSU Undergraduate Research and Creativity Symposium (aka "Discover Day")

2021- Phi Zeta Research Emphasis Day Virtual Meeting

Soileau A, Schaumburg J, Costa V, Boyd A, Moeller C, Withers SS. Decreasing the inhibitory effects of myeloid cells on lymphocyte function using all-trans retinoic acid (ATRA) in dogs with cancer (Poster Presentation)

Costa V, Soileau A, Liu CC, Moeller C, Carossino M, Langohr I, Balasuriya U, Withers SS. Exploring the association of intratumoral immune cell infiltrates with histopathologic grade in canine mast cell tumors (Poster Presentation) – 1st prize for clinical report by a house officer

Bauman A, Moeller C, Boyd A, Soileau A, Schaumburg J, Pucheu-Haston C, Domaracki C, Welborn N, Withers SS. Memory T-lymphocyte subsets in dogs in health and with cancer and inflammatory disease (Poster Presentation)

Flow cytometry gating strategy for identifying naive and memory subsets of T-lymphocytes in the blood of dogs.

2020- Veterinary Cancer Society Virtual Meeting

Withers SS, Moeller C, Liu CC, Merkle J, Looper J, Quick C, Baham S, Subramanian R, Kousoulas KG. Effect of stimulator of interferon genes (STING) signaling in canine and human osteosarcoma on cytokine/chemokine expression after radiation exposure (Poster Presentation)

Costa V, Soileau A, Liu CC, Moeller C, Carossino M, Langohr I, Balasuriya U, Withers SS. Exploring the association of intratumoral immune cell infiltrates with histopathologic grade in canine mast cell tumors (Poster Presentation)

Soileau A, Costa V, Moeller C, Boudreaux BL, Withers SS. The effect of arginase on canine lymphocyte function and its modulation by vincristine chemotherapy in dogs with lymphoma (Poster Presentation)

Flow cytometry gating strategy for identifying granzyme B expression by cytotoxic T-lymphocytes in the blood of dogs.