Striving to understand the immune system and HIV: Q&A with a CHS alumna

Since graduating from Chaska High School in 2000, Nichole Klatt has immersed herself in science.

She is currently a doctoral student at the University of Pennsylvania, researching the human immunodeficiency virus, which results in AIDS.

She recently presented her research at one of the largest HIV conferences in the world.

The Herald decided to touch base with Klatt and ask her about the research, and life after CHS.

(A portion of this Q&A ran in the March 6 print edition of the Chaska Herald. It is printed here in its entirety.)

What have you been doing since high school graduation?

I graduated from the University of Minnesota, Duluth, with a degree in biology and chemistry in May 2004.

At UMD I performed research testing the anti-microbial and anti-viral properties of tea plant components (i.e. epigallocatechin gallate) on pathogenic bacteria and herpes viruses.

I received three grants from the University of Minnesota through the Undergraduate Research Opportunities Program (UROP) to perform this work, and I presented this research at undergraduate research conferences in Salt Lake City, Utah, and Indianapolis, Ind. This research experience prepared me for graduate school, as well as ensuring I wanted to make a career out of disease research.

I began graduate school at Emory University in Atlanta, Ga., in June 2004 as a Ph.D. student in the Immunology and Molecular Pathogenesis program, part of the Graduate Division of Biological and Biomedical Sciences.

After performing three laboratory rotations pertaining to infectious disease research, I joined the laboratory of Dr. Guido Silvestri, M.D. for my thesis research studying human immunodeficiency virus (HIV) using non-human primate models (more detail below).

In 2006, Dr. Silvestri accepted a faculty position at the University of Pennsylvania, and in June 2006 I moved from Atlanta to Philadelphia to finish my thesis research at UPenn.

I’m scheduled to graduate in January 2009 with my Ph.D. in immunology and molecular pathogenesis.

What first piqued your interest in science?

Seventh-grade science class with (Mr.) Jerry Loader at Chaska Middle School. I found myself mesmerized by dissections and learning about biology - Mr. Loader embraced this passion I found and helped me to get a scholarship to science camp over the summer (so dorky, I know!).

This piqued my interest, which continued to grow throughout high school, where I took all the biology courses I could before doing post-secondary at Normandale community college to continue with more challenging courses in biology (I did a year and a half post-secondary, earning 31 college credits before graduating high school).

During this time I read the book “The Hot Zone” by Richard Preston (published 1994), which is about infectious viruses, specifically Ebola. Reading this book opened me up to the virus research field, which I became passionate about. I am absolutely fascinated by the complexity and ingenuity of the smallest “living” thing we know of! This is why I began research in the virology field in college, moving into viral immunology in graduate school.

How did you begin research in HIV?

At Emory University I had multiple labs to choose from where I could perform virology research, however I became especially interested in Guido Silvestri’s lab for multiple reasons.

First, my passion for studying a virus which affects so many people (over 30 million people are infected worldwide); second, I found the research in Dr. Silvestri’s lab both practical and fascinating, with impressive implications for HIV therapies; and third, Dr. Silvestri is an amazing thesis advisor - joining a lab with a good mentor is vital to success in graduate school.

What is your specific field if interest within HIV research?

My thesis is entitled “Mechanisms of Immune Dysfunction during HIV Pathogenesis.”

The major reason it has been so difficult to produce an effective vaccine against HIV is because it is extremely complex and “outsmarts” our immune system, making it very difficult to protect against.

HIV infection causes major dysfunction of our immune system, eventually resulting in acquired immunodefiency syndrome (AIDS).

I utilize monkey models to study these dysfunctions of the immune system during simian immunodeficiency virus (SIV) infection of non-human primates (AKA the “monkey version” of HIV).

The first part of my thesis I used sooty mangabeys, a natural host for SIV, which is actually where HIV-2, a predominantly African strain of HIV, came from after cross-species transmission to humans. Studying these natural hosts is important because these animals are infected with SIV, but stay healthy without progressing to AIDS, thus providing an example of animals which evolved to live (normal lifespans) with SIV.

I specifically studied the interactions between the immune system and the virus in order to determine what dictates viremia during natural non-pathogenic infection of SIV (this manuscript is currently submitted to the Journal of Clinical Investigation - hopefully it will be accepted and published this spring/summer).

The second half of my thesis research (which the talk below is part of) I’m using rhesus macaques, which we use as a model for HIV infection, as SIV infection of these monkeys results in a disease progression strikingly similar to HIV infection of humans.

By performing experiments in these SIV-infected animals, we have a model to very accurately measure the immune responses that are elicited during SIV infection.

Using this animal model allows us to ask specific questions using experimental approaches and treatments not permissible in human studies, to better understand HIV infection and elucidate possible therapeutic interventions and vaccination approaches.

You recently gave a presentation at an AIDS conference entitled “Depletion of CD8+ T Cells Does Not Change the in vivo Life Span of Infected Cells during Pathogenic SIV Infection of Rhesus Macaques.” In laymen’s terms what does this mean?

This is a very complex study, and is very difficult to put into laymen’s terms, but briefly, this study is aimed to better understand the role of the immune system during HIV infection in order to determine the best target for an HIV vaccine.

The majority of HIV vaccines produced (and every HIV vaccine sent to clinical trials) have been aimed to elicit a specific cell response (CD8+ T cells) because these cells kill virus-infected cells in order to protect against HIV infection. Because current HIV vaccine approaches have not been efficacious when brought to clinical trials, we aimed to re-evaluate the role of these cells during pathogenic SIV infection of rhesus macaques (see above).

We found that during SIV/HIV infection, CD8+ T cells are dysfunctional, namely that they do not directly affect the lifespan of HIV-infected cells, and thus may not be the most appropriate target for future HIV vaccine approaches.

This study is important because it has direct implications for how HIV vaccines are produced and it has made clear that further understanding of HIV pathogenesis is needed in order to advance vaccine research.

What is the significance of the conference?

The Conference on Retroviruses and Opportunistic Infections (CROI) is one of the largest HIV conferences worldwide. Conferences such as CROI are extremely important, as they allow for thousands of HIV researchers, M.D.s (clinical) and pharmaceutical researchers all to gather and share knowledge. Important collaborations, networking and awareness of different fields of HIV research result from this conference, which helps to further our understanding of HIV.Straight from the CROI Web site (www.retroconference.org): “The 15th Conference on Retroviruses and Opportunistic Infections is a scientifically focused meeting of the world’s leading researchers working to understand, prevent, and treat HIV/AIDS and its complication.

”What do you find interesting in HIV research?HIV infection is a major challenge - both because over 30 million people are infected worldwide and because it is such a difficult virus to treat and prevent. Both of these aspects are interesting to me - I want to help humanity by furthering our understanding of HIV, while I myself am fascinated by the complexity of the virus.

What do you spend most of your time doing (ie., computer work/lab work/crunching numbers)?

All of the above! Because I perform major studies in a non-human primate model, about equal amounts of time go into brainstorming and planning these studies, and then executing the studies (actual “bench” work, where I spend hours under a biosafety hood processing the samples), and finally performing data analysis on the huge amounts of data we collect (mostly computer work).

What do you hope to do after you earn your Ph.D.?

Right now my major options are to continue disease research at the National Institutes of Health (NIH) in Bethesda, Md., or the Centers for Disease Control (CDC) in Atlanta, Ga. I plan to continue HIV and infectious disease research.

What are some misperceptions about HIV research?

One frustration is that people tend to think that after 20 years of research the HIV research field has not done much.

However, highly active antiretroviral therapies (HAART) and small molecule inhibitors all were developed in laboratories like my own, and have made a tremendous impact on the disease course. The majority of people today can lead very normal lives after HIV infection, and are living with the virus longer and longer before succumbing to AIDS.

This technology is only getting better with further research and understanding, and I have no doubt that in the years to come, people will live fairly normal lives after HIV infection.

However this only applies to countries such as the U.S. where these drugs are available. Unfortunately, in countries such as Africa, which harbor the vast majority of infected people (over 20 million), HAART is not widely available or affordable, and thus a vaccine is a better option.

I think the greatest challenge with people not in the HIV field is a lack of understanding of just how complex HIV is. Vaccinations such as small pox and rabies were really a lot of luck - there was little understanding of these viruses when the vaccines were made, and they’re both large viruses without the mutation capabilities that HIV has, which makes it very difficult to vaccinate or treat HIV.

Thus the simple trial and error techniques used to effectively make vaccines in the past does not work with HIV. Unfortunately, due to public (i.e. government) pressure, many vaccines have gone forward to clinical trials and failed because we just do not have adequate understanding of the virus yet and what we need to do to make an effective HIV vaccine, thus causing doubt and speculation in the non-HIV research world.

I am 100 percent positive, though, that with continued research into the pathogenesis of HIV we will at some point find correlates of protection that will allow us to make an effective HIV vaccine someday.

What precautions do you need to take in the lab when working with the virus?

I work in biosafety level 2 and 3 conditions. On a normal day with samples, I work in a contained room (designated for biosafety), in a biosafety hood which has negative airflow so no air circulation comes outside the hood. I am fully gowned to protect my clothing, and I wear safety goggles and double glove.

We have multiple safety measures for disposal and containment of the samples we work with. We are very well trained to ensure our safety when working with this infectious virus, and there is little safety risk since we are properly educated.

What do you do in your spare time?

Spare time? What is that?!?!? Ha, ha. When I do get spare time, I enjoy relaxing with my fiancé, Jason Moon. I’m a huge advocate of vacations - I think time away from this crazy world is important once and awhile, so we try to get away every now and then to go camping or get to the beach.

I’m also a bit of a card shark; I enjoy playing Texas hold’em whenever I get a chance.

Nichole Klatt

Age: 25

Family: parents Gary and Anne Klatt; siblings Jacob Klatt (class of 2003), Brian Klatt (class of 2003) and Katie (Klatt) Marchione (class of 1998); fiancé Jason Moon.

Graduated from CHS: 2000

Researching: Human immunodeficiency virus

Hobbies: Camping, the beach, Texas hold’em