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Test Tube to Bedside: The RUSH Way

Lena Al-Harthi, PhD

by Lena Al-Harthi, PhD

“Why do I care about how bacteria respond to viral infections? Shouldn’t we be studying diseases that are impacting the quality of life of humans or those that are killing us?” Those are questions that may have been uttered in the not-so-recent past.

In 1987, Yoshizumi Ishino, PhD, cloned clustered regularly interspaced short palindromic repeats, or CRISPRs, from bacteria with the help of his colleagues. CRISPERs are repeating DNA sequences in bacteria. It was not until 13 years later that Francisco Mojica, PhD, and his team found that these sequences were similar to those found in bacteriophages, which are viruses that infect bacteria. They showed that bacteria with these CRISPERs cannot be infected by a bacteriophage, essentially showing that bacteria can edit foreign DNA sequences and protect themselves against viral infection.

This knowledge is now applied to the exciting field of gene editing. Imagine the possibilities of being able to splice or edit a gene that causes cystic fibrosis, fragile X-syndrome, Huntington’s disease, some cancers and HIV. We may not have to imagine for long — gene editing successfully corrected a genetic mutation in an embryo harboring a gene that causes cardiac disease. In our lifetime, we may likely see CRISPR put into practice to treat inherited diseases in adults.

The possibilities for this technology are endless, and it all started with rigorous studies in a test tube to show the presence of these DNA sequences and how bacteria use them to avoid viral infections.

I share this story to show how scientific knowledge cannot be limited. Fundamental understanding of biology among organisms is interconnected and useful for guiding discovery from test tube to bench side. 

At RUSH, we are at the interface of science informing clinical care.

I joined RUSH after completing my doctorate in microbiology from George Washington University and my dissertation research in the lab of Robert Gallo, MD, the co-discoverer of HIV. I selected RUSH to join a team of HIV investigators composed of scientists and physician-scientists working together to understand the interface between HIV and its host. I was supported by the Mark Weiss Memorial Clinic for Infectious Diseases as a fellow. Mark lost his life to HIV in the 1980s, regrettably prior to our current advances in HIV therapy. His family recognized the value of research and established this fellowship at RUSH in his honor.

Today I am a professor and the chair of the Department of Microbial Pathogens and Immunity and the director of the RUSH Initiative to Maximize Student Development, or RUSH-IMSD. RUSH-IMSD is a National Institutes of Health-funded doctoral training grant (T32) for underrepresented minority students. I found RUSH to be a highly supportive environment that nurtured and provided me with opportunities to contribute back in two core critical missions, research and education.

My research focuses on HIV and host interactions, with a special emphasis on bridging basic and clinical science in the HIV and AIDS field. I probe mechanistic questions that are clinically relevant to HIV and AIDS, specifically studying how signaling pathways impact HIV and host interactions in the brain, which enables me to better understand the mechanisms of HIV pathogenesis.

HIV invades the brain within two weeks of infection and causes neurocognitive impairment in 30-50% of people living with it. I also study how the brain is a sanctuary site for HIV. Francis Collins, MD, PhD, former director of the National Institutes of Health, recently highlighted work from my laboratory stating: “HIV cure strategies must address the role of the brain after a study found brain cells can harbor HIV and spread it to other organs in the body via immune cells.” These studies aim to evaluate host and virus interaction with the goal of informing therapeutic strategies to cure HIV and ameliorate or reduce HIV-associated neurocognitive impairment.

Equally important to me is the training of the next wave of scientists. RUSH-IMSD is a response to a national call to address disparities in the training of underrepresented minorities in science. Our efforts have increased the number of doctoral underrepresented minority graduates from RUSH and created an environment within our labs that reflects our general population.

As a chair of a department that I started as a fellow in, I have tremendous pride in facilitating and advocating for the success of my faculty and students. We have a group of talented researchers working on an array of host-pathogen interactions, such as HIV, Zika, SARS-CoV-2, flu, schistosomiasis and cryptosporidium, and bridging this knowledge to other conditions, including aging and Alzheimer’s disease.

As RUSH alumni, I ask you to join me in advocating for research and training of our next generation of scientists who will tackle impactful questions that will better our human condition. There are several opportunities to show your support for RUSH Medical College research. You can sponsor an annual doctorate or master’s student stipend, establish a fellowship to support a post-doctorate fellow to engage in research in one of our labs in an area of research that resonates with you or make a donation to partially support keeping a lab viable. I appreciate your thoughtfulness and hope to see you during RUSH University All Alumni Weekend on Oct 21-22, celebrating RUSH University’s 50th anniversary. More information can be found on the All Alumni Weekend event page.

We are #RUSHproud.

 

Lena Al-Harthi, PhD is Chairperson of the Department of Microbial Pathogens and Immunity, RUSH Medical College; Thomas J. Coogan Sr., MD, Chair of Immunology in the Department of Microbial Pathogens and Immunity, RUSH Medical College; and Director of the RUSH Initiative to Maximize Student Development (Rush-IMSD).