Howard Hall 596
Dr. O. Colin Stine is a world renowned bacterial disease geneticist and epidemiologist. He uses genetic information to make novel observations about diarrheal pathogens and complex human disorders like stroke. His researh has three foci: 1) bacterial interactions in diarrhea, 2) cholera and 3) stroke.
Bacterial interactions in diarrhea
Dr Stine was one of the first to recognize that in countries with less sophisticated water purification and sanitary sewer systems, children are often infected with more than more pathogen. Lindsay et al 2011 (PMID 21470448) revealed that for patients admitted to hospital in Kolkata, the combination of multiple pathogens was not random. In order to better understand the nature of diarrheal infections Dr. Stine incorporated the idea that pathogen load is essential. The quantitative PCR methodology revealed first that Shigella was more wide spread than previously thought occurring in 80% of children without diarrhea and that there was a threshold above which Shigella was the likely cause of diarrhea (Lindsay et al 2013 PMID 23536399). In order to examine all of the microbiota, his group began anlyzing the small subunit of ribosomal RNA gene (16S). In order to perform legitimate statistical tests, he and his team developed appropriate normalization and zero correction methods (Paulson et al Nature Methods PMID 24076764). Their initial survey (Pop et al. PMID 24995464) has implicated selected Streptococcus species as possible novel pathogens. In addition, his group has developed the methodology for estimating the effect size of associations between bacterial species, their analysis of their quantitative PCR data for Shigella combined with their 16s data revealed that there are four Lactobacillus taxa that will decrease the odds of diarrhea in children with sufficient Shigella to have diarrhea by a factor of two. (Lindsay et al.2015 PMID: 25625766). Currently Dr Stine is working on a previously unrecognized Streptococcus pathogen for diarrhea and strains of Lactobacillus that inhibit the growth of Shigella.
Dr Stine developed multilocus tandem repeat analysis methods for V. cholerae, compared them to whole genome sequencing and applied both methods to epidemiological surveys. Kachwamba 2017 PMID 28219321 characterized isolates from outbreaks in Tanzania and identified genetically separate outbreaks in the same location and genetically identical outbreaks in different regions. Bwire et al. 2018 PMID: 29864113 extend these studies into Uganda and identified a new transmission event from South Asia to east Africa. George et al 2017 PMID: 29178823 demonstrated that both person-to-person and household source water-to-person transmission occurred and in different proportions in different outbreaks.
Dr. Stine is part of the ongoing search for genes associated with stroke. Stroke like other complex human disorders clearly have a significant genetic component. If genes associated with these disorders can be identified, then novel treatment or diagnostic methods may be understood. Over time the size of the populations examined has increased. The most recent results to emerge from the merging of consortia are i) there are 32 stroke-related loci implicated by GWAS in a large population (Nature Genetics 2018 PMID 29531354) and ii) COL4A2 is associated with lacunar ischemic and deep intracerebral hemorrhage strokes (Neurology 2017 PMID 28954878).
Dr Stine has had over 100 graduates student spend 3 or more months in his laboratory including over 20 from low income countries.
bacterial infections in diarrhea, cholera, stroke
Bwire G, Sack DA, Almeida M, Li S, Voeglein JB, Debes AK, Kagirita A, Buyinza AW, Orach CG, Stine OC. Molecular characterization of Vibrio cholerae responsible for cholera epidemics in Uganda by PCR, MLVA and WGS. PLoS Negl Trop Dis. 2018 Jun 4;12(6):e0006492. PMID: 29864113
Lindsay B, Oundo J, Hossain MA, Antonio M, Tamboura B, Walker AW, Paulson JN, Parkhill J, Omore R, Faruque AS, Das SK, Ikumapayi UN, Adeyemi M, Sanogo D, Saha D, Sow S, Farag TH, Nasrin D, Li S, Panchalingam S, Levine MM, Kotloff K, Magder LS, Hungerford L, Sommerfelt H, Pop M, Nataro JP, Stine OC. Microbiota that affect risk for shigellosis in children in low-income countries. Emerg Infect Dis. 21(2):242-50. 2015 PMID: 25625766
George CM, Mahamud Rashid M, Almeida M, Saif-Ur-Rahman KM, Monira S, Bhuyian MSI, Hasan K, Mahmud TT, Li S, Brubaker J, Perin J, Rahman Z, Mustafiz M, Sack DA, Sack RB, Alam M, Stine OC. Genetic relatedness of Vibrio cholerae isolates within and between households during outbreaks in Dhaka, Bangladesh BMC Genomics 2017 Nov 25;18(1):903. PMID: 29178823
Kachwamba Y, Mohammed AA, Lukupulo H, Urio L, Majigo M, Mosha F, Matonya M, Kishimba R, Mghamba J, Lusekelo J, Nyanga S, Almeida M, Li S, Domman D, Massele SY, Stine OC. Genetic Characterization of Vibrio cholerae O1 isolates from outbreaks between 2011 and 2015 in Tanzania. BMC Infect Dis. 2017 17:157. PMID: 28219321
Pop M, Paulson JP, Chakraborty S, Astrovskaya I, Lindsay BR, Li S, Bravo HC, Harro C, Parkhill J, Walker AW, Walker RI, Sack DA, Stine OC, Individual-specific changes in the human gut microbiota after challenge with enterotoxigenic Escherichia coli and subsequent ciprofloxacin treatment, BMC Genomics 2016 PMID 27277524 304 citations
George CM, Mahamud Rashid M, Almeida M, Saif-Ur-Rahman KM, Monira S, Bhuyian MSI, Hasan K, Mahmud TT, Li S, Brubaker J, Perin J, Rahman Z, Mustafiz M, Sack DA, Sack RB, Alam M, Stine OC. Genetic relatedness of Vibrio cholerae isolates within and between households during outbreaks in Dhaka, Bangladesh BMC Genomics 2017
Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.(>200 co-authors) Nat Genet. 2018 Apr;50(4):524-537. PMID: 29531354