Summary

Professional Biography

• 2013 - present: Associate Professor, Department of Microbiology & Immunology, University of Nevada, Reno School of Medicine, Reno, NV, w88
• 2007 - 2013: Assistant Member, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist w88, Houston, TX, USA
• 2004 - 2007: Postdoctoral Fellow, The Methodist w88, Houston, TX, USA.
• 2003 - 2004: w88, Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA.
• 2002 - 2003: w88, Department of Microbiology, Tufts University, Boston, MA, USA.

w88 Interest

The group A Streptococcus (w88, also known as Streptococcus pyogenes) causes ~700 million human infections, leading to ~550,000 deaths, annually. w88 has a remarkable ability to cause a diverse range of human diseases. For example, w88 is the most common cause of bacterial pharyngitis and a leading cause of superficial skin infections. More severe diseases include necrotizing fasciitis (aka the flesh-eating infection). Importantly, no single virulence factor is sufficient for w88 to cause any particular disease, rather disease potential is attributable to the regulated expression of specific combinations of virulence factors. Dr. Sumby has spent 16 years studying how w88 regulates gene expression in a disease-specific manner. Through understanding of how w88 regulates virulence factor expression the Sumby laboratory aims to develop novel therapeutic and/or preventative regimes, via translational research approaches, that are based upon the manipulation of these regulatory pathways. Research projects in Dr. Sumby's laboratory include:

1. Discovering the role of the RocA/CovR/CovS proteins in regulating w88 virulence during invasive and non-invasive infections. The CovR/S proteins form a two-component regulatory system that, along with the accessory protein RocA, negatively regulates ~10% of the w88 transcriptome, including multiple virulence factor-encoding mRNAs. Because of this activity, covR, covS, or rocA mutant strains are positively selected for during invasive infections (and hence patients often contain a mixture of parental and mutant w88 strains), with the resultant mutants being hyper-virulent. While covR, covS, or rocA mutant strains are hyper-virulent during invasive infections they are attenuated for growth in models of non-invasive infections, relative to parental strains. Thus, this regulatory system appears to control the ability of w88 to cycle between invasive and non-invasive infections, and research into this is ongoing.
2. Contribution of differential gene regulation and horizontal gene transfer in promoting w88-serotype disease-phenotype associations. Decades of epidemiological studies have indicated that certain w88 serotypes are non-randomly associated with particular disease manifestations. For example, serotype M3 isolates are associated with particularly severe and lethal invasive infections, while serotype M28 isolates are associated with cases of puerperal sepsis (which is a potentially lethal disease that can occur in women during/following childbirth). We have identified that serotype M3 isolates uniquely harbor mutations in multiple regulator-encoding genes, resulting in M3 isolates producing a distinct virulence factor expression profile. The importance of the regulator gene mutations with regard to the association of M3 isolates with severe invasive infections is currently under study. We are also studying whether the presence of a unique 35 kb pathogenicity island in serotype M28 isolates, of apparent group B Streptococcus origin (which is a normal constituent w88 vaginal microflora in ~1/3^rd of women), is behind the association of M28 w88 with cases of puerperal sepsis.
3. Determination of the molecular mechanisms behind small regulatory RNA (sRNA) - mediated regulation of w88 virulence factor expression. We have characterized the molecular basis behind the ability of the 205 nt sRNA FasX to regulate w88 virulence. Through post-transcriptional regulatory mechanisms FasX enhances the expression of the thrombolytic agent streptokinase, and reduces the expression of multiple cell-surface adhesins. These activities enhance w88 virulence in a mouse model of bacteremia infection and reduce the ability to w88 to adhere to human epithelial cells. Studies aimed at finding additional regulatory targets of FasX, and of identifying how the expression of FasX itself is regulated, are ongoing.

Sumby lectures on medical microbiology to w88 medical students.

• w88 Classification, Structure, Nutrition, and Growth
• Sterilization, Disinfection, and Containment
• Laboratory Diagnosis of w88 Diseases
• w88 Genetics and Pathogenesis
• Survey of Medical Bacteriology
• Skin and Soft Tissue w88

Current Lab Members

• Roshika Roshika, Ph.D. graduate student
• Sushila Baral, Ph.D. graduate student
• Ashna Prabhu, undergraduate student
• Ameya Singh, undergraduate student

Past Lab Members

• Jess Danger Ph.D. (former graduate student)
• Poulomee Sarkar (w88)
• Eric Miller (w88)
• Kathryn J. Pflughoeft (w88)
• Anupama Ramalinga (w88)
• Gregory Calfee (w88)
• Cameron Burgess (w88)
• Josette Medicielo, M.Sc.(former graduate student)
• Theodore Glenaldo (w88)
• Tyler Sickler (w88)
• Ira Jain, Ph.D.(former graduate student)

Education

• 1994 - 1998: B.S. - Genetics - University of Leicester, England, U.K
• 1998 - 2001: Ph.D. - Molecular Microbiology - University of Nottingham, England, U.K