Suresh K. Nagumalli, Ph.D.

a. Use of advanced spectroscopic techniques (LC-MS and NMR) to evaluate the toxicology of complex mixtures using multivariate statistical methods like PCA and PLS.

b. Development and validation of qualitative and quantitative analytical methods for determination of fatty acid composition in vegetable oils using LC-MS.

a. Designed the studies to access myelostimulatory and toxicological properties of eleven accessions belonging to three different species of Echinacea obtained from USDA, Ames, IA and herbco.com.
b. Identified that lipopolysaccharides as hypothesized by others (Pugh et al. 2013) and increase in bone marrow early precursor cells (CFU-GEMM) are not responsible for myelostimulation with Echinacea.
c. Conducted H&E, apoptosis, and PAS diastase staining of liver of Echinacea-treated rats to inform mechanism of loss of relative liver weight and serum alkaline phosphatase.
d. Applied multivariate statistics (PCA, PLS, & OPLS-DA) and identified the regions of 1H-NMR (bins) correlating with the bone marrow progenitor stimulating effect and decrease in alkaline phosphatase exhibited by Echinacea.

Dysregulation of epidermal growth factor receptor (EGFR)/human epidermal growth factor-2 (HER2) family is a hallmark of aggressive breast cancer. Small-molecule tyrosine kinase inhibitors are among the most effective cancer targeted treatments. (−)-Oleocanthal (OC) is a naturally occurring phenolic secoiridoid lead from extra-virgin olive oil with documented anti-cancer activities via targeting mesenchymal epithelial transition factor (c-Met). Dysregulation of c-Met promotes aggressiveness to breast cancer-targeted therapies. Lapatinib (LP) is an FDA-approved dual EGFR/HER2 inhibitor for HER2-amplified breast cancer. HER2-Positive tumor cells can escape targeted therapies like LP effects by overexpressing c-Met. Combined OC-LP treatment is hypothesized to be mechanistically synergistic against HER2-overexpressing breast cancer. Combined sub-effective treatments of OC-LP resulted in synergistic anti-proliferative effects against the HER2-positive BT-474 and SK-BR-3 breast cancer cell lines, compared to OC or LP monotherapy. Antibody array and Western blot analysis showed that combined OC-LP treatment significantly inhibited EGFR, HER2, and c-Met receptor activation, as well as multiple downstream signaling proteins, compared to individual OC or LP treatment. OC-LP Combination significantly inhibited invasion and migration of breast cancer cells through reduced activation of focal adhesion kinase (FAK) and paxillin. Combined treatment of OC-10 mg/kg with LP-12.5 mg/kg suppressed more than 90% of BT-474 tumor cells growth in a nude mouse xenograft model, compared to individual OC or LP treatment. Activated c-Met, EGFR, HER2, and protein kinase B (AKT) were significantly suppressed in combination-treated mice tumors, compared to OC or LP monotherapy. This study reveals the OC future potential as combination therapy to sensitize HER2-overexpressing breast cancers and significantly reduce required doses of targeted HER family therapeutics.