EvIL- Evolutionary Medicine

Making the connection

Ecological and evolutionary principles are central elements in organismal health. An understanding of ecology and evolution can greatly improve our ability to face some of the largest threats to human health including as antibiotic resistance, zoonotic transmission, or cancer. Our lab strives to leverage its phylogenomic expertise to aid in this endeavour

We collaborate closely with other groups and have worked on topics that include the evolution of key oncogenes, the response of cancer to specific treatment, and most recently on the durability of the immune response following infection by SARS-CoV-2

Using evolution to determine SARS-CoV-2 reinfection risks

Throughout the COVID-19 pandemic, there was much uncertainty about how long immunity lasts after someone who is unvaccinated is infected with SARS-CoV-2. Working together with Dr. Jeffrey Townsend at the Yale School of Public Health and several other collaborators, we developed an innovative approach rooted in phylogenetic comparative methods to provide an answer: strong protection following natural infection is short-lived.

We analyzed known reinfection and immunological data from the close viral relatives of SARS-CoV-2 that cause “common colds” — along with immunological data from SARS-CoV-1 and Middle East Respiratory Syndrome. Leveraging evolutionary principles, we were able to model the risk of COVID-19 reinfection over time. Reinfections can and have happened, even shortly after recovery. And they will become increasingly common as immunity wanes and new SARS-CoV-2 variants arise. The COVID-19 pandemic made it clear how interconnected we are, and these findings underscore the importance of vaccination to break transmission chains

This model and findings were published long before reinfections were common or data on reinfection was available and have proven to be highly accurate

What about vaccination?

We have expanded our model to assess the risk of future infection by SARS-CoV-2 over time following vaccination from several vaccines. This provides a comparative basis for natural and vaccine mediated immunity as well as quantitative evidence that supports current booster schedules.

Lab initiatives

Expanding to other human infecting viruses
Oncogene evolution
Viral and bacterial surveys in marine environments
Evolutionary techniques for pandemic preparedness

Projecting the seasonality of endemic COVID-19

It is clear that COVID-19 will become an endemic disease. However, when to expect surges of cases in different parts of the world is less clear.

On the one hand, SARS-CoV-2 could follow a pattern similar to other seasonal respiratory viruses such as the flu. On the other hand, it is possible the low levels of circulation occur year round. This would be similar to several other non-seasonal respiratory viruses

Using incidence data collected across the Northern Hemisphere from the closest evolutionary relatives of SARS-CoV-2, we projected what an endemic COVID-19 might look like and just published a preprint

Phylogeny and cancer

To effectively guide research in cancer biology it is important to place oncogenes into a phylogenetic context. We recently finished work on anaplastic lymphoma kinase (ALK), a gene present in species that span humans to fruitflies with a high degree of structural conservation.

ALK has been identified as a potential target for therapeutic development due to its association with tumorigenesis in neuroblastoma, non small cell lung cancer, anaplastic large-cell lymphoma, breast and renal cell carcinomas. Our work demonstrated that the leukocyte tyrosinekinase (LTK) gene and ALK have switched functionality between ray-finned fishes and sarcopterygians (tetrapods, lungfish, and coelacanth) and that the interacting partners for these genes are not homologous between vertebrates and non-vertebrates. These findings have major implications for translational medicine

In addition to this type of comparative genomics studies, we also recently worked several collaborators to use the phylogeny of a tumor in conjunction with patient history to reveal the selective response to different therapies. This type of approach has tremendous power for revealing general responses to therapies, and could pave the way fo getting ahead of cancer's evolutionary trajectory