Kevin J Gaffney

Interests

Research

My research seeks to combine my Ph.D. work in computational drug design and synthetic chemistry with my post-doctoral work in pharmacology to develop novel GPCR-targeting therapeutics and characterize their biological efficacy to deliver the drugs to patients in need.

Courses

No activities entered.

Scholarly Contributions

Journals/Publications

• Gaffney, K., Jadhav, S., Reyes‐Reyes, E. M., Rodgers, K. E., & Soto, M. (2021).

  Mitigation of cognitive decline and brain pathology after transaortic constriction by Mas agonists

  . Alzheimer's & Dementia, 17(S9). doi:10.1002/alz.055661
• Soto, M., Gaffney, K. J., & Rodgers, K. E. (2019). Improving the Innate Immune Response in Diabetes by Modifying the Renin Angiotensin System. Frontiers in immunology, 10, 2885.
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  Patients with Type 2 Diabetes Mellitus (T2DM) suffer from a higher incidence and severity of pulmonary infections. This is likely due to immune impairment and structural abnormalities caused by T2DM-induced oxidative stress (OS) and chronic inflammation. Modulation of the Renin Angiotensin System (RAS) through blockade of the actions of angiotensin II (AII), or inducing the protective pathway, has the potential to reduce these pathological pathways. The effects of Angiotensin 1-7 [A(1-7)] and NorLeu-A(1-7) [NorLeu], ligands of the protective RAS, on the innate immune response were evaluated in the mouse model of T2DM. Only NorLeu treatment reduced the structural pathologies in the lung caused by T2DM. A decreased in bactericidal activity and phagocytosis in diabetic animals was also observed; both A(1-7) and NorLeu treatment restored these functions. Myeloid progenitor CFUs were reduced and neutrophil/progenitor OS was increased in saline-treated mice, and was reversed by A(1-7) and NorLeu treatment. These results demonstrate the adverse effects of diabetes on factors that contribute to pulmonary infections and the therapeutic potential of protective RAS peptides. Overall, RAS-modification may be a viable therapeutic target to treat diabetic complications that are not addressed by glucose lowering drugs.
• Gaffney, K. J., Jadhav, S. S., Rodgers, K. E., & Soto, M. (2018).

  A(1-7) reduces pathologies associated with SLE in MRL-lpr mice

  . The Journal of Immunology, 200(1_Supplement), 175.2-175.2. doi:10.4049/jimmunol.200.supp.175.2
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  Abstract Patients with Systemic Lupus Erythematosus (SLE) suffer from a chronic inflammatory autoimmune disease that causes damage to various organ systems. Even with the array of current treatments, patients with lupus are still in need of effective therapies to treat this complex, multi-system disease. Recent studies of the Renin Angiotensin System (RAS), widely known for its role in blood pressure regulation, have uncovered immunomodulatory effects. One of the more recently discovered components of RAS, angiotensin (1-7) [A(1-7)], is a bioactive peptides that affects various systems. In our study, MRL-lpr mice were treated daily with saline or A(1-7) for 6 weeks starting at 8 weeks of age. Proteinuria was monitored throughout the duration of the study. MRL-lpr mice treated with saline had higher levels of proteinuria compared to the MRL/MpJ- control mice, and A(1-7) treated MRL-lpr mice. A glomerulonephritis score revealed that the MRL-lpr mice had significant glomerular pathologies compared to MRL-MpJ mice of the same age. A(1-7) treatment significantly reduced the glomerular pathologies in the MRL-lpr mice. Treatment with A(1-7) reduced the size of both inguinal and axillary lymph nodes in MRl-lpr mice, and levels of anti-dsDNA IgG compared to the saline treated MRL-lpr mice. Treatment with A(1-7) also significantly reduced the severity of cutaneous pathologies resulting in only mild inflammation and hair loss compared to the saline treated MRL-lpr mice. Daily systemic treatment with A(1-7) significantly ameliorated disease in one of the most severe mouse models of SLE, making Mas agonists a potential target for future SLE therapies.
• Gaffney, K. J., Rodgers, K. E., Weinberg, M., & Soto, M. H. (2018). Development of angiotensin II (1-7) analog as an oral therapeutic for the treatment of chemotherapy-induced myelosuppression. Haematologica, haematol.2018.193771.
• Gaffney, K. J. (2015). Molecular characterization of the boron adducts of the proteasome inhibitor bortezomib with epigallocatechin-3-gallate and related polyphenols.. Organic & biomolecular chemistry.
• Gaffney, K. J. (2014). Abstract 1811: Evaluation of anti-CXCR2 small molecule inhibitors as novel chemotherapy targeting the Interleukin-8 pathway in colorectal cancer. Cancer Research.
• Gaffney, K. J. (2012). Inhibition of the function of class IIa HDACs by blocking their interaction with MEF2. Nucleic Acids Research.
• Gaffney, K. J. (2012). Preferential killing of triple-negative breast cancer cells in vitro and in vivo when pharmacological aggravators of endoplasmic reticulum stress are combined with autophagy inhibitors.. Cancer letters.
• Gaffney, K. J. (2011). Enhancement of photodynamic therapy by 2,5-dimethyl celecoxib, a non-cyclooxygenase-2 inhibitor analog of celecoxib. Cancer Letters.
• Gaffney, K. J. (2010). Antiangiogenic Activities of 2,5-Dimethyl-Celecoxib on the Tumor Vasculature. Molecular Cancer Therapeutics.
• Gaffney, K. J. (2010). Cytotoxic effects of celecoxib on Raji lymphoma cells correlate with aggravated endoplasmic reticulum stress but not with inhibition of cyclooxygenase-2. Leukemia Research.
• Gaffney, K. J. (2009). Enhanced killing of chemo-resistant breast cancer cells via controlled aggravation of ER stress. Cancer Letters.
• Gaffney, K. J. (2009). Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood.
• Gaffney, K. J. (2008). COX-2 inhibition is neither necessary nor sufficient for celecoxib to suppress tumor cell proliferation and focus formation in vitro. Molecular Cancer.