Ramesh Kumar Wali

Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-t...

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Background Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States. There is an increasing need for the identification of biomarkers of pre-malignant and early stage CRC to improve risk-stratification and screening recommendations. In this study, we investigated the possibility of metabolic and mitochond...

Alterations in high-order chromatin, with concomitant modulation in gene expression, are one of the earliest events in the development of colorectal cancer (CRC). Cohesins are a family of proteins that modulate high-order chromatin, although the role in CRC remains incompletely understood. We, therefore, assessed the role of cohesin SA1 in CRC biol...

Background: We have previously reported that colonic pericryptal microvascular blood flow is augmented in the premalignant colonic epithelium, highlighting the increased metabolic demand of the proliferative epithelium as a marker of field carcinogenesis. However, its molecular basis is unexplored. In this study, we assessed the expression of a re...

MicroRNAs (miRNAs) have been shown to be reliable early biomarkers in a variety of cancers including that of lung. We ascertained whether the biomarker potential of miRNAs could be validated in microscopically normal and easily accessible buccal epithelial brushings from cigarette smokers as a consequence of lung cancer linked 'field carcinogenesis...

Nuclear alterations are a well-known manifestation of cancer. However, little is known about the early, microscopically-undetectable stages of malignant transformation. Based on the phenomenon of field cancerization, the tissue in the field of a tumor can be used to identify and study the initiating events of carcinogenesis. Morphological changes i...

Current fecal tests (occult blood, methylation, DNA mutations) target minute amounts of tumor products among a large amount of fecal material and thus have suboptimal performance. Our group has focused on exploiting field carcinogenesis as a modality to amplify the neoplastic signal. Specifically, we have demonstrated that endoscopically normal rec...

Colorectal cancer (CRC) screening tests often have a trade-off between efficacy and patient acceptability/cost. Fecal tests (occult blood, methylation) engender excellent patient compliance but lack requisite performance underscoring the need for better population screening tests. We assessed the utility of microRNAs (miRNAs) as markers of field ca...

Gastrointestinal (GI) malignancies are notorious for frequently progressing to advanced stages even in the absence of serious symptoms, thus leading to delayed diagnoses and dismal prognoses. Secondary prevention of GI malignancies through early detection and treatment of cancer-precursor/premalignant lesions, therefore, is recognized as an effecti...

Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality underscoring the need for safe and effective chemopreventive strategies. Targeting epidermal growth factor receptor (EGFR) is attractive in that it is an early critical event in HNSCC pathogenesis. However, current agents lack efficacy or have unacceptable tox...

We employed polarization-gating spectroscopy in the azoxymethane-treated rat model of colon carcinogenesis and found differences in the shape of the refractive index correlation function that correlated with risk of neoplasia. This marker has potential in predicting tumor development.

Polarization-gated spectroscopy is an established method to depth-selectively interrogate the structural properties of biological tissue. We employ this method in vivo in the azoxymethane (AOM)-treated rat model to monitor the morphological changes that occur in the field of a tumor during early carcinogenesis. The results demonstrate a statistical...

Infections from enteric bacteria such as enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic Escherichia coli (EHEC) are a public health threat worldwide. EPEC and EHEC are extracellular pathogens, and their interaction with host surface receptors is critical to the infection process. We previously demonstrated that polyethylene glycol (...

Spectroscopic techniques have demonstrated that in the microscopically normal mucosa, there is an increase in mucosal micro-circulation in patients harboring neoplasia elsewhere in the colon (i.e. marker of field carcinogenesis). However, the physiological and molecular basis of this early increase in blood supply (EIBS) has not been elucidated. We...

This study was undertaken to examine the gender-sensitivity and chemopreventive responsiveness of celecoxib on intestinal stem-like cells as a biomarker of colon carcino-genesis, using the MIN mouse model. Male and female MIN mice (6-7-weeks old) were randomized to either control diet or to a diet supplemented with celecoxib (1,500 ppm). The animal...

Epithelial proliferation, critical for homeostasis, healing, and colon cancer progression, is in part controlled by epidermal growth factor receptor (EGFR). Proliferation of colonic epithelia can be induced by Citrobacter rodentium infection, and we have demonstrated that activity of tumor suppressor FOXO3 was attenuated after this infection. Thus...

Polyethylene glycol (PEG) is a safe and effective chemopreventive agent against colorectal carcinogenesis in cell culture, animal models and human subjects. Although the precise molecular mechanism is unclear, we previously reported that PEG suppresses colonic epithelial proliferation. As cellular proliferation is driven by complex G1-S phase trans...

Low-coherence enhanced backscattering (LEBS) spectroscopy is a light scattering technique which uses partial spatial coherence broadband illumination to interrogate the optical properties at sub-diffusion length scales. In this work, we present a post-processing technique which isolates the hemoglobin concentration at different depths within a samp...