Houra Merrikh, Ph.D.

DNA Replication, mutagenesis, & evolution

Research Keywords: DNA replication, mutagenesis, evolution, and anti-microbial resistance

Research Specialty: Replication-transcription conflicts and the consequences on mutagenesis related to bacterial and human diseases.

Research Description: DNA replication is a fundamental process for life in all cells. However, genome duplication is not a smooth process due to obstacles that the replication machinery faces as it moves along DNA. DNA replication and transcription occur simultaneously on the same template leading to conflicts between the two machineries that carry out these processes. Conflicts stall replication forks, lead to genome instability, mutagenesis, and the formation of deleterious three stranded nucleic acid structures known as R-loops. The Merrikh lab’s first branch is focused on understanding how cells deal with conflicts and identifying essential factors that are involved in the resolution of these encounters. For our studies, we use bacteria and human cells and take various approaches including genetics, molecular biology, biochemistry, bioinformatics, and single molecule imaging.

The Merrikh lab also has a second branch which is focused on the problem of anti-microbial resistance (AMR). AMR causes over 1.4 million deaths globally each year, and is on the rise such that it is predicted to surpass deaths caused by cancer by the year 2050. Drug resistance is a process that is driven by evolution. Over the years, we identified active mechanisms that cells harbor that increase mutation rates, accelerating evolution. Although many groups are focused on resolving the problem of AMR through the discovery of new therapeutic agents that kill cells, this approach by itself cannot eradicate this disease because resistance stems from evolution. We are taking a completely different approach to tackle this problem. We have committed to finding and utilizing small molecules that can inhibit the activity of mutagenic factors and stop the evolution of resistance development in bacteria altogether.

Current projects in the lab:

• Developing a high resolution map of genomic loci that experience conflicts and the degree to which each locus is impacted.
• Identification and characterization of factors that deal with the consequences of R-loop structures.
• Identify anti-evolution compounds that can be developed into drugs for use in the clinic to fight AMR.
• Further characterize anti-evolution compounds that we have identified through SAR and medicinal chemistry approaches.

Significance: Understanding the basic biology behind essential cellular functions is necessary to develop new strategies to fight diseases such as cancer and AMR. Our work collectively bridges basic biology and translational research to facilitate our understanding of how diseases come about, and based on these discoveries, develop novel strategies to fight clinical problems.

PubMed Listing of Dr. Merrikh’s Publications

POSTDOCTORAL POSITION AVAILABILITY AND DETAILS: Postdoctoral positions are available. For consideration, please submit your CV and two letters of recommendation to Dr. Merrikh.