Faculty Profile


Michael Letko

Michael Letko

Assistant Professor

michael.letko@wsu.edu

 

Biography:
Dr. Letko is a molecular virologist with a research focus on cross-species transmission and viral-host interactions. He graduated from Skidmore College in 2011 with a B.A. in molecular biology and then obtained his PhD at the Icahn School of Medicine at Mount Sinai in New York City. As a graduate student in the Department of Microbiology, Michael worked in the laboratory of Dr. Viviana Simon studying viral-host co-evolution of lentiviral species barriers. During these formative years he developed a deep appreciation of how viral diversity at the smallest scales can dramatically influence viral phenotypes and how viruses and their hosts co-evolve. In 2015 he defended his thesis on the interactions of host APOBEC3 proteins and lentiviruses and then moved to Hamilton, Montana, where he started a post-doctoral fellowship in the Laboratory of Virology at the NIH’s Rocky Mountain Laboratories (RML).

Dr. Vincent Munster’s Virus Ecology Section at RML provided a unique opportunity for Michael to experience virus ecology from a range of scientific perspectives. In 2017, he traveled to Republic of Congo as part of Dr. Munster’s ongoing field research program sampling African fruit bats for filoviruses. He also had the privilege of working at the Jordan University of Science and Technology as part of a separate project screening dromedary camels for MERS-CoV. Additionally, he worked closely with other scientists and veterinarians in RML’s BSL4 facility to help evaluate vaccines for MERS-CoV and Nipah in small animals, study transmission and stability of MERS-CoV, and assess host competency of bats to Nipah and SARS-related coronavirus, WIV1.

These experiences had a strong impact on the types of scientific questions Michael asks. Expanding further on his molecular virology training, Michael’s current work is focused on building new molecular tools tailored to understanding various aspects of cross-species transmission. This work has begun to elucidate the zoonotic potential for betacoronaviruses, has demonstrated the receptor for SARS-CoV-2 and many of these tools are now being distributed around the world to aid scientists in testing vaccines and antiviral drugs for SARS-CoV-2.

In the summer of 2020, Dr. Letko joined the faculty at the Paul G. Allen School at WSU and opened the laboratory of functional viromics. His lab is centered on the concept of testing in the laboratory, groups of related, novel viruses within the expansive virome, for their ability to cross species barriers.

Michael is dedicated to promoting a diverse work environment, with the belief that our scientific communities should be a greater reflection of our society. He strives to ensure the work produced by his laboratory represents not only rigorous academic pursuit, but also different voices, views and beliefs. All are welcome in the Laboratory of Functional Viromics.

Personal Statement:

In high school, I had a biology teacher tell me that evolution did not happen because “nobody in your family photos ever had a tail!”

Needless to say, I started college thinking I would be a theater major. I was rejected from the school’s improv teams right away, so I took some neuroscience courses and started working in a developmental neurobiology lab pulling little glass straws into hair-thin needles and then carefully injecting single-celled fish embryos with drugs. What a rush. Naturally, my focus shifted from theater to molecular biology.

I was accepted to the summer undergraduate program at Mt. Sinai in my junior year of college, just after I finished taking a course in virology. Fascinated by viruses, I did a summer rotation in Peter Palese’s influenza lab that year, became completely hooked on virus research, and applied to the graduate program. Five years later I defended my thesis on HIV and was eager to apply what I had learned to less-studied emerging pathogens. This was also around the time of the devastating 2014-2016 Ebolavirus outbreak in western Africa, and just shortly after the 2012 MERS-CoV outbreak in the middle east, which maybe also had something to do with my choice to study these types of viruses.

My favorite aspect of science is discovery – finding something new and learning from it. There is still so much that we do not understand about the invisible microbes that cohabit our planet. Everything we can learn about the viruses circulating in nature will be crucial toward responding to, and one day even preventing, the next emerging pathogen.

Education, Training and Awards:

Post-doctoral fellow, Virus Ecology Section, Laboratory of Virology, RML (2016-2020)
Graduate student, Department of Microbiology, Icahn School of Medicine at Mount Sinai (2011-2016)
B.a. molecular biology and genetics, Skidmore College (2007-2011)

General Research / Expertise:

The majority of emerging viral pathogens in humans arose from cross species transmission. While viromics studies have uncovered sequences for thousands of novel animal viruses, almost nothing is known about the function of these sequences: if these viruses can transmit to humans or cause disease. The laboratory of functional viromics utilizes synthetic biology and molecular engineering to develop platforms that assess zoonotic potential of novel, pre-emergent viruses. Importantly, these platforms are scalable, allowing for simultaneous analysis of multiple viruses. This work will help elucidate species barriers to viral transmission and aid in pandemic preparedness by dramatically improving risk assessment of zoonosis for newly discovered viruses.

Research Contributions:

  • Development of a time and cost-effective platform to screen lineage B betacoronaviruses for their ability to use different host receptors and infect human and other mammalian-derived cell lines
  • Screened the host-receptor preferences for the majority of currently-known lineage B betacoronaviruses showing that several viruses in this group, found circulating in bats, are capable of infecting human cells
  • Used to effectively demonstrate, in the laboratory, the host-r eceptor for SARS-CoV-2, in under 12 days from the release of the first viral genome.

Research Details:

Current global virome sequencing projects suggest coronaviruses represent one of the largest families of viruses, found in most mammals around the world. As humans increase their expansion into new environments, they come into closer contact with different carrying novel viruses. Domestcated animals only further exacerbate this threat, as they can often serve as intermediate hosts between humans and the wildlife we encroach upon. Thus, it is imperative we improve our understanding for what viruses pose the greatest risk to transmitting to humans and domestic and peri-domestic species.

While sequencing technologies are constantly improving and expanding our ability to detect viral sequences circulating in nature, there is a deficit in downstream laboratory studies on these viruses. This is primarily due to the difficulty in actually isolating and culturing these viruses. Further, synthesis of even full viral genes to study with in vitro experiments can be cost and time-prohibitive. Dr. Letko’s research is centered around the concept of building unique tools and approaches to assess the zoonotic potential of viruses circulating in nature.

One approach currently being pursued by Dr. Letko’s group is to test key functional domains involved in coronavirus cross-species transmission. These domains are much smaller regions of the viral genome than whole genes, and are therefore more cost-effective to have synthesized in bulk from different viruses. The synthesized domains are then tested in various cell-culture based experiments to assess basic molecular biology underpinning the zoonotic potential of these viruses.