About

Antonio Baines is an Associate Professor and Adjunct Associate Professor at North Carolina Central University. His prime focus is to validate novel molecular targets, such as oncogenic PIM kinases, for potential therapeutic intervention in pancreatic cancer and other cancers. He also tests novel PIM kinase inhibitors in combination with chemotherapy. His work aims to advance understanding of molecular targets in cancer treatment, contributing to the development of targeted therapies.

Research topics

• Medicine
• Internal medicine
• Cancer research
• Biochemistry
• Cell biology
• Biology
• Chemistry

Selected publications

• AUM-302, a novel triple PIM/PI3K/mTOR inhibitor, synergizes with RAS inhibition and impedes the growth of pancreatic ductal adenocarcinoma spheroids and organoids

  UNC Libraries · 2026-03-12

  articleOpen access

  Pancreatic ductal adenocarcinoma (PDAC) is a significant contributor to cancer-related deaths in the United States. The limited number of well-defined, druggable targets in PDAC has hindered the development of effective treatments. The PIM/PI3K/mTOR pathways, which regulate cell growth, apoptosis, metabolism, and protein synthesis, are often dysregulated in PDAC, leading to various transformed phenotypes, including unchecked cell proliferation. Here, we demonstrate that the triple kinase inhibitor AUM-302 exhibits strong inhibitory efficacy against PDAC growth in 3D formats, including spheroids and organoids. Experiments were conducted using BxPC-3, Capan-2, MIA PaCa-2, and PANC-1 human PDAC cell lines, hF37 2D organoid-derived PDAC cell line, and primary (hF37, hF31, hF44, hT1) and metastatic (hM1a) patient-derived pancreatic cancer organoids. Single- and dual-kinase inhibitors TP-3654, GDC-0941, BEZ-235, respectively, and DMSO were used as controls. The synergy studies were performed using AUM-302 and the RAS inhibitor RMC-6236. Our results showed that AUM-302 significantly inhibited the viability and proliferation of PDAC cell spheroids and organoids more effectively than the controls. The activity of mTOR, AKT, and S6 pathways was decreased as measured by the expression levels of the phosphorylated proteins in hT1 and hM1a organoids after 24 h of AUM-302 treatment, suggesting that AUM-302 reduced the activity of these kinases. Finally, combinatorial assays revealed synergy between AUM-302 and the RAS inhibitor RMC-6236 in reducing the growth of hT1 and hM1A organoids. By blocking kinase activity, AUM-302 demonstrates potent inhibition in PDAC cell lines and organoids across two 3D culture formats. Treatment with this novel triple PIM/PI3K/mTOR inhibitor may also chemosensitize PDAC to other cancer therapies, such as RAS inhibitors.

  PublisherDOI

• Coordinated Transcriptional Increases in Cell Wall Synthesis Genes in Neisseria gonorrhoeae Lacking the Lytic Transglycosylase, ltgA

  Current Microbiology · 2025-05-06

  articleOpen access

  Lytic transglycosylase A in Neisseria gonorrhoeae cleaves the β-1,4-glycosidic bond between peptidoglycan (PG) monomers to liberate 1,6-anhydro-PG fragments that are either recycled or released as cytotoxic fragments. To gain further insight into the effect of LtgA on cellular processes in Neisseria gonorrhoeae, we performed a proteomic analysis comparing wild-type and an isogenic ltgA null mutant strain. Proteins were separated by two-dimensional gel electrophoresis and identified by MALDI-TOF mass spectrometry, which revealed several proteins that were increased in their level of expression upon loss of LtgA. The most notable changes corresponded to enzymes related to aminosugar and pyrimidine metabolism. Quantitative real-time RT-PCR of mRNA from a ltgA null strain confirmed increased transcription of genes encoding enzymes involved in UDP-N-acetylglucosamine (UDP-GlcNAc) synthesis, a major precursor in PG and lipooligosaccharide (LOS) synthesis, during normal growth conditions and following exposure to penicillin. We also found that the ltgA mutant strains were more susceptible to β-lactam antibiotics, vancomycin, and the human-cathelicidin antibacterial peptide, LL-37, than their corresponding wild-type parental strains. Our results suggest that increased expression of enzymes responsible for production UDP-GlcNAc is an adaptive response due to inactivation of ltgA and/or exposure to penicillin.

  PublisherOA PDFDOI

• Tu1151: AUM-302, A NOVEL TRIPLE PIM/PI3K/MTOR INHIBITOR, SYNERGIZES WITH KRAS INHIBITION AND IMPEDES THE GROWTH OF PANCREATIC DUCTAL ADENOCARCINOMA SPHEROIDS AND ORGANOIDS

  Gastroenterology · 2025-05-01

  article
  PublisherDOI

• Application of Integrated Drug Screening/Kinome Analysis to Identify Inhibitors of Gemcitabine-Resistant Pancreatic Cancer Cell Growth

  UNC Libraries · 2024-07-27

  articleOpen access
  PublisherDOI

• Cancer and Carcinogenesis

  Elsevier eBooks · 2024-01-01

  book-chapter1st authorCorresponding
  PublisherDOI

• Sa1206 AUM-302, A NOVEL TRIPLE PIM/PI3K/MTOR INHIBITOR, IS A POTENT PANCREATIC CANCER GROWTH INHIBITOR

  Gastroenterology · 2023

  • Cancer research
  • Medicine
  • Chemistry
  PublisherDOI

• AUM302, a novel triple kinase PIM/PI3K/mTOR inhibitor, is a potent in vitro pancreatic cancer growth inhibitor

  PLoS ONE · 2023 · 7 citations

  • Cancer research
  • Biology
  • Medicine

  Pancreatic cancer is one of the leading causes of cancer deaths, with pancreatic ductal adenocarcinoma (PDAC) being the most common subtype. Advanced stage diagnosis of PDAC is common, causing limited treatment opportunities. Gemcitabine is a frequently used chemotherapeutic agent which can be used as a monotherapy or in combination. However, tumors often develop resistance to gemcitabine. Previous studies show that the proto-oncogene PIM kinases (PIM1 and PIM3) are upregulated in PDAC compared to matched normal tissue and are related to chemoresistance and PDAC cell growth. The PIM kinases are also involved in the PI3K/AKT/mTOR pathway to promote cell survival. In this study, we evaluate the effect of the novel multikinase PIM/PI3K/mTOR inhibitor, AUM302, and commercially available PIM inhibitor, TP-3654. Using five human PDAC cell lines, we found AUM302 to be a potent inhibitor of cell proliferation, cell viability, cell cycle progression, and phosphoprotein expression, while TP-3654 was less effective. Significantly, AUM302 had a strong impact on the viability of gemcitabine-resistant PDAC cells. Taken together, these results demonstrate that AUM302 exhibits antitumor activity in human PDAC cells and thus has the potential to be an effective drug for PDAC therapy.

  PublisherDOI

• Inhibition of Ras for cancer treatment: the search continues

  UNC Libraries · 2021-07-01

  articleOpen access

  The RAS oncogenes (HRAS, NRAS and KRAS) comprise the most frequently mutated class of oncogenes in human cancers (33%), stimulating intensive effort in developing anti-Ras inhibitors for cancer treatment.

  PublisherDOI

• The oncogenic kinase Pim-1 is modulated by K-Ras signaling and mediates transformed growth and radioresistance in human pancreatic ductal adenocarcinoma cells

  UNC Libraries · 2020-11-01 · 5 citations

  articleOpen access

  Oncogenic Pim-1 kinase is upregulated in multiple solid cancers, including human pancreatic ductal adenocarcinoma (PDAC), a highly lethal disease with few useful treatment options. Pim-1 is also transcriptionally induced upon oncogenic K-Ras-mediated transformation of the human pancreatic ductal epithelial (HPDE) cell model of PDAC. Given the near ubiquitous presence of mutant K-Ras in PDAC and its critical role in this disease, we wished to study the effects of oncogenic K-Ras signaling on Pim-1 expression, as well as the role of Pim-1 in growth transformation of PDAC cells. Pim-1 protein levels were upregulated in both PDAC cell lines and patient tumor tissues. Furthermore, ectopic oncogenic K-Ras increased Pim-1 expression in human pancreatic nestin-expressing (HPNE) cells, a distinct immortalized cell model of PDAC. Conversely, shRNA-mediated suppression of oncogenic K-Ras decreased Pim-1 protein in PDAC cell lines. These results indicate that oncogenic K-Ras regulates Pim-1 expression. The kinase activity of Pim-1 is constitutively active. Accordingly, shRNA-mediated suppression of Pim-1 in K-Ras-dependent PDAC cell lines decreased Pim-1 activity, as measured by decreased phosphorylation of the pro-apoptotic protein Bad and increased expression of the cyclin-dependent kinase inhibitor p27Kip1. Biological consequences of inhibiting Pim-1 expression included decreases in both anchorage-dependent and -independent cell growth, invasion through Matrigel and radioresistance as measured by standard clonogenic assays. These results indicate that Pim-1 is required for PDAC cell growth, invasion and radioresistance downstream of oncogenic K-Ras. Overall, our studies help to elucidate the role of Pim-1 in PDAC growth transformation and validate Pim-1 kinase as a potential molecular marker for mutated K-Ras activity.

  PublisherDOI

• Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine

  UNC Libraries · 2020-11-01 · 1 citations

  articleOpen access

  Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a 5-year survival rate of only 6%. Although the cytosine analog gemcitabine is the drug commonly used to treat PDAC, chemoresistance unfortunately renders the drug ineffective. Thus, strategies that can decrease this resistance will be essential for improving the dismal outcome of patients suffering from this disease. We previously observed that oncogenic Pim-1 kinase was aberrantly expressed in PDAC tissues and cell lines and was responsible for radioresistance. Furthermore, members of the Pim family have been shown to reduce the efficacy of chemotherapeutic drugs in cancer. Therefore, we attempted to evaluate the role of Pim-3 in chemoresistance of PDAC cells. We were able to confirm upregulation of the Pim-3 oncogene in PDAC tissues and cell lines vs. normal samples. Biological consequences of inhibiting Pim-3 expression with shRNA-mediated suppression included decreases in anchorage-dependent growth, invasion through Matrigel and chemoresistance to gemcitabine as measured by caspase-3 activity. Additionally, we were able to demonstrate that Pim-1 and Pim-3 play overlapping but non-identical roles as it relates to gemcitabine sensitivity of pancreatic cancer cells. To further support the role of Pim-3 suppression in sensitizing PDAC cells to gemcitabine, we used the pharmacological Pim kinase inhibitor SGI-1776. Treatment of PDAC cells with SGI-1776 resulted in decreased phosphorylation of the proapoptotic protein Bad and cell cycle changes. When SGI-1776 was combined with gemcitabine, there was a greater decrease in cell viability in the PDAC cells vs. cells treated with either of the drugs separately. These results suggest combining drug therapies that inhibit Pim kinases, such as Pim-3, with chemotherapeutic agents, to aid in decreasing chemoresistance in pancreatic cancer.

  PublisherDOI

Recent grants

• NIH Grant SC2CA137845

  NIH · $280k · 2012

Frequent coauthors

• Albert S. Baldwin

  24 shared

• Brian K. Bednarski

  The University of Texas MD Anderson Cancer Center

  24 shared

• Han Jo Kim

  Lenox Hill Hospital

  21 shared

• Catherine D. White

  North Carolina Agricultural and Technical State University

  12 shared

• Jen Jen Yeh

  University of North Carolina at Chapel Hill

  10 shared

• Sam M. Witherspoon

  North Carolina Central University

  10 shared

• Michael G. Cobb

  North Carolina Central University

  9 shared

• Lee M. Graves

  7 shared

Labs

• Curriculum in Toxicology & Environmental MedicinePI

Education

• Ph.D., Toxicology

  University of North Carolina at Chapel Hill

  1990

• M.S., Toxicology

  University of North Carolina at Chapel Hill

  1986

• B.S., Toxicology

  University of North Carolina at Chapel Hill

  1984