Posted November 7, 2014
Dr. Mansour Mohamadzadeh, University of Florida
PRCRP FY11 Discovery Award
Dr. Mansour Mohamadzadeh was awarded a Fiscal Year 2011 Peer Reviewed Cancer Research Program (PRCRP) Discovery Award to study the interaction of a novel strain of L. acidophilus and its potential role in protective immunity against colon cancer. Within the human gut, over 100 trillion of different microorganisms, composed mainly of bacteria, reside symbiotically. These microorganisms are essential for the healthy function of the gut and provide several benefits to the human host, including maintenance of proper metabolism, production of vitamins, and protection against chronic inflammation, a known risk factor of colon cancer. Protection against chronic inflammation is achieved through interactions between the bacterial surface proteins and host cells lead to host cells producing anti-inflammatory cytokines in response to prolonged inflammation. Insufficient levels of these anti-inflammatory signals may lead to chronic pathogenic inflammation and promote carcinogenesis.
In previous studies, Dr. Mansour Mohamadzadeh and colleagues observed that a molecule called lipoteichoic acid (LTA) expressed on the surface of the bacteria, L. acidophilus, which is a major component of the natural beneficial microbiota in the colon, is strongly involved in promoting inflammatory immune responses in host cells. Based on these observations, Dr. Mohamadzadeh hypothesized that eliminating LTA expression from the surface of L. acidophilus via genetic engineering may enhance the bacteria's ability to normalize pathogenic immune responses in the host cells and reduce inflammation in the colon. With support from the PRCRP Discovery Award, Dr. Mohamadzadeh tested a series of genetically modified LTA-deficient L. acidophilus strains, including one named NCK2025, in a mouse model of colonic polyps. When orally administered, NCK2025 reversed the pathologic inflammation in the precancerous colonic polyps and prevented malignant progression in these mice. Dr. Mohamadzadeh is currently working toward identifying the critical bacterial gene-products, including surface layer protein A (SlpA) responsible for its anti-inflammatory properties to translate these research findings into clinical development.
Khazaie K, Zadeh M, Khan MW, Bere P, Gounari F, Dennis K, Blatner NR, Owen JL, Klaenhammer TR, Mohamadzadeh M. Abating colon cancer polyposis by Lactobacillus acidophilus deficient in lipoteichoic acid. Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10462-7.
Yang T, Owen JL, Lightfoot YL, Kladde MP, Mohamadzadeh M. Microbiota impact on the epigenetic regulation of colorectal cancer. Trends Mol Med. 2013 Dec;19(12):714-25.
Lightfoot YL, Yang T, Sahay B, Mohamadzadeh M. Targeting aberrant colon cancer-specific DNA methylation with lipoteichoic acid-deficient Lactobacillus acidophilus. Gut Microbes. 2013 Jan-Feb;4(1):84-8.