OHTN Profile: Lena Serghides

Dr. Lena Serghides is an assistant scientist at the Toronto General Research Institute and a scientist at the Sandra Rotman Centre for Global Health at the University Health Network. She received her Ph.D. from the Institute of Medical Sciences at the University of Toronto. Her research focuses on deciphering the mechanisms contributing to increased adverse pregnancy events in HIV-positive women, especially understanding the impact of HIV infection and HIV antiretroviral treatment on placenta and fetal development. She also has an interest in HIV-malaria co-infection.

OHTN Interview

Q: Tell us a little about yourself - where did you do your training? What did you do it in?

A: I have always loved science. My grandfather was a trained chemist and we spent lots of time together talking science. When it was time for university - I went into business (my parents run their own business and I was planning to get involved). I lasted 2 years - then I begged the Chair of Biology to let me transfer. After that everything felt right. I finished my undergrad at Wilfrid Laurier University in biology, and then did my PhD training at the University of Toronto with Dr. Kevin Kain. I chose to work with Dr. Kain for two reasons. His area of expertise was malaria, which I thought was a great disease to study, and he was so excited about what he did that his enthusiasm was contagious. I did a post-doc training with Dr. Tania Watts at the department of Immunology at the University of Toronto, where I got my first taste of HIV research.


Q: Please tell us about your current academic/institutional positions and affiliations as they relate to research in HIV:

A: I am currently a Scientist at the Sandra Rotman Centre for Global Health, and I am an Assistant Scientist at the Toronto General Research Institute at the University Health Network. I am also very involved with IHPREG (the Interdisciplinary HIV Pregnancy Research Group). This is a group of Ontario based multidisciplinary researchers (social, basic, community, clinicians, etc) with an interest in HIV and pregnancy.


Q: Your work focuses on both HIV and Malaria, but HIV seems to be a relatively new area of research for you - how did you come to develop an interest in HIV?

A: It was a bit of a fortuitous evolution. I did my training in the malaria field. But HIV and malaria are diseases that overlap geographically, mostly in sub-Saharan Africa where close to 30 million people are living with HIV and about 200 million people are infected with malaria each year. One of my projects related to HIV and malaria co-infection in pregnancy, which got me interested in HIV. Around the same time I had my first child, which got me even more interested in pregnancy. I was then lucky enough to rekindle an old relationship with Dr. Mona Loutfy, who is the head of the Women and HIV program at Women's College, and was initiating the IHPREG group. The final (and very important) event was that I received a Junior Investigator Development Award from OHTN to study HIV in pregnancy. So all the elements came together to allow me to move into the HIV field, which I am very excited about.


Q: Tell us a bit about the OHTN funded research you're currently pursuing related to angiogenesis and adverse pregnancy outcomes in women living with HIV:

A: Women that are living with HIV tend to have more complications during their pregnancy. This could be related to their infection, but also to the type of antiretroviral drugs they are taking. Combination antiretroviral therapy has been a great thing, enabling women to live longer, fuller lives that include safe childbearing. However, there is some evidence to suggest that HIV-positive women on combination therapy have a higher risk for some adverse pregnancy outcomes, such as having a pre-term delivery and having a low birth weight baby. I am trying to understand how and why this happens. One of the theories we are investigating is that the angiogenic process is altered in these women and that this contributes to their adverse pregnancy outcomes. Angiogenesis is the process of forming blood vessel, and it is a very important process for the development of a healthy placenta. A healthy placenta is needed to provide the baby with all the nutrients and oxygen it needs to develop properly. If the blood vessels are not properly formed, then the placenta will not function optimally, and the development of the baby may suffer.

One of the ways we can check if the angiogenic process is altered is by measuring certain angiogenic factors in the blood. As part of this research project we are following HIV-positive and HIV-negative pregnant women, taking blood sample from them throughout their pregnancy. We will use these blood samples to measure the levels of angiogenic factors and see if there are differences between HIV-positive and HIV-negative women, if there are differences between antiretroviral drug regimens, and if there is a relation between these factors and the pregnancy outcome. We are also studying this process in the lab using placenta cells and mice. With these experiments we can ask very specific mechanistic questions that are not possible to ask in humans, but can help us to better understand what is happening in our HIV-positive pregnant women.

Ultimately, we are hoping to use this research to develop diagnostic tools that can identify women with a high-risk pregnancy as early as possible, so they can be given extra care to ensure that they have the best outcome possible. We are also hoping to identify antiretroviral regimens that are most suitable for use during pregnancy.


Q: Can you talk about any early results you're seeing (in general terms)?

A: We are still in the early phase of recruiting our pregnancy cohort, however I can tell you that even with the small number of HIV-positive women we have recruited so far, we are observing a fairly high number of adverse pregnancy outcomes. This suggests to me that this is a worthwhile pursuit, and that our work is addressing an issue that is relevant to these women.

We do have some early results that suggest that certain antiretroviral drugs have an affect on angiogenic factors and alter the function of placenta cells. We are also developing a mouse pregnancy model to study the effect of antiretroviral drugs on pregnancy outcome, and so far we have been able to replicate the pre-term and low birth weight outcomes we see in HIV-positive women in this model. We are now excited to use this model to figure out how these drugs cause these adverse events, and if there is any way we can prevent them from happening.


Q: You are a Co-Principal Investigator on a CIHR team grant called 'Interdisciplinary HIV Pregnancy Research Group: Care and Research to Optimize HIV-positive Women's Health during Preconception, Pregnancy and Motherhood' - can you tell us a bit about what this program is about?

A: We were very surprised and excited that we received this grant. CIHR issued a call for emerging teams to study maternal health. We (Mona Loutfy, Mark Yudin, and I) put together a letter of intent. CIHR selected 7 teams that were invited to apply, and we were number 7. We knew our chances weren't great but we put the application together. By the end the grant had 3 co-principal investigators and 43 co-investigators. The focus was entirely on HIV-positive women, and it included projects relevant to preconception, pregnancy, and motherhood. CIHR funded 2 projects and ours was number two - we were elated that CIHR chose to fund a maternal health project dedicated to HIV-positive women. The aims of the program are to optimize the care of HIV-positive couples (where one or both partners are HIV-positive) that are contemplating pregnancy; to better understand the impact of antiretroviral therapy on the mother and fetus during pregnancy; and to explore the likelihood of depression and to understand the unique needs of HIV-positive mothers. With this grant we are also developing new collaborations between people whose work focuses on maternal health and HIV. A significant portion of the funds are dedicated to training and mentoring new HIV researchers. Part of this training includes a mentorship program that will help create bidirectional mentorship relationships between researchers, students, and community members. We also have an extensive knowledge translation plan that includes the creation of an IHPREG website - which is launching this week, and an annual conference.


Q: Can you talk about how the community is involved in your research? What is your perspective of the value added by involving community in the development, implementation, and diffusion of research?

A: The community is an integral part of my research and my involvement with IHPREG has greatly facilitated this. Through IHPREG, we have a dedicated Community Advisory Board that meets regularly to discuss IHPREG projects including mine. These discussions help shape my research plan, and focus my work on issues that are relevant to the community. For example, I increased my focus on drug safety during pregnancy because that issue was important to community members. Our findings are still quite preliminary, but we have an extensive plan for sharing our data with the community.


Q: Can you tell us briefly about your other research interests (both related to, and not related to, HIV)?

A: One of my other interests is HIV and malaria co-infection and in trying to understand how HIV changes the way the immune system fights malaria. HIV-positive people are much more like to get infected with malaria, to have higher parasite burdens, and to get more severe malaria disease - and we don't completely understand why this is.

I am also still interested in malaria, and specifically on developing therapies for a severe complication of malaria called cerebral malaria. If you develop cerebral malaria you have a 30% chance of dying even if you are receiving the best anti-malarial drugs available. We have been working on developing therapies that target the immune system, because we believe that an over-activated immune response contributes to the development of this syndrome. One of the potential therapies I have been working on since my PhD is a class of drugs currently used for the treatment of type II diabetes.

Recent Publications

  1. Eszter Papp, Lena Serghides. (2012). Angiogenic factor imbalance in cART exposed trophoblast cells. Canadian Association of HIV Research Conference. Montreal, Quebec.
  2. Constance Finney, Kodjo Ayi, James Wasmuth, Prameet Sheth, Rupert Kaul, Mona Loutfy, Kevin Kain, Lena Serghides. (2011). Chronic HIV Infection Impairs Phagocytosis of Malaria Parasites OHTN Annual Research Conference. Toronto, Ontario.
  3. Constance Finney, Kodjo Ayi, James Wasmuth, Prameet Sheth, Rupert Kaul, Mona Loutfy, Kevin Kain, Lena Serghides. (2011). The effect of HIV infection on malaria: down-regulating innate inflammatory responses. OHTN Annual Research Conference. Toronto, Ontario.

Current Funding

Interdisciplinary HIV pregnancy research group: care and research to optimize HIV positive women's health during preconception, pregnancy, and motherhood
Amount: $ 900,000
Duration: 2011-2014
Funding Source: CIHR Emerging Team Grant - Maternal Health
Role: Principal Investigator, with Co-Principal Investigators Mona Loutfy and Mark Yudin

Abstract: Anti-HIV drug therapy has been very successful at reducing the rate of death for those living with HIV; as well as reducing the rate of vertical HIV transmission from mother to child. These successes, combined with the fact that many HIV-positive people in Canada are of childbearing age, have led many HIV-positive women and HIV-negative female partners of HIV-positive men to become pregnant. This has been confirmed by an increase in the number of HIV-positive women having children. Also the HIV-positive community has said that pregnancy and pregnancy planning are important issues to them. Although prevention of vertical transmission is an important topic, there are several others that are crucial when considering pregnancy and pregnancy planning in the context of HIV. These include the prevention of HIV transmission between sex partners (known as horizontal transmission), healthy pre-conception counselling and managing infertility issues. This is area that has been under-researched and has tremendous opportunity. Also, because there are an increasing number of pregnancies amongst HIV-positive women, there are now tremendous opportunities for research in all the maternal health stages and HIV including the pregnancy, labour and delivery and the postpartum/motherhood phases. The main goal of this Emerging Team Grant in Maternal Health for women infected with and affected by HIV is to form an Ontario program of research, teaching, mentoring and knowledge translation regarding the care of these women during the three phases of maternal health: 1) before pregnancy, 2) during pregnancy, and 3) postpartum, during motherhood. This program will help to create partnerships among researchers, clinicians, policy makers and community members and help to teach them about how our study findings may impact maternal health in the context of HIV.


Angiogenesis and Adverse Pregnancy Outcomes In HIV-Positive Women
Amount: $ 260,000
Duration: 2009-2014
Funding Source: Ontario HIV Treatment Network - Junior Investigator Development Award
Role: Principal Investigator

Abstract: HIV-positive pregnant women have a greater chance of having complications with their pregnancy. This is a problem of great importance to these women and their infants, however, it has received very little attention from the research community. A healthy placenta is very important to a healthy pregnancy. The ability of the placenta to deliver sufficient oxygen and nutrient to the developing fetus relies on it having a properly developed blood supply network. Several factors are involved in dictating how this blood supply network is developed. We will examine the levels of these factors in the blood of HIV-positive women during their pregnancy and see if they correlate with the pregnancy outcome. We will compare these factors in both HIV-positive and HIV-negative women to examine if having HIV affects these factors. These experiments may lead to tests that can be performed early in the pregnancy to identify women that will have bad pregnancy outcomes.


PPAR-gamma agonists for the treatment of cerebral malaria - tweaking the host response to save brains
Amount: $ 100,000
Duration: 2011-2013
Funding Source: Grand Challenges Canada - Rising Stars
Role: Principal Investigator

This project aims to rescue a child with cerebral malaria from death or long-term cognitive impairment, by protecting their brain. The idea is to use PPARg agonists, a type of anti-diabetic drug, to treat cerebral malaria. PPARg agonists have neuro-protective and neuro-regenerative properties, that may help to reduce and repair malaria-caused brain injury. Watch the video.


Angiogenesis and adverse pregnancy outcomes in women with HIV
Amount: $ 300,000
Duration: 2011-2013
Funding Source: Ontario HIV Treatment Network - Research Operating Grant
Role: Principal Investigator

Abstract: HIV-positive pregnant women have a greater chance of having complications with their pregnancy, such as pre-term delivery and low birth weight infants. This is a problem of importance to these women and their infants, however, it has received very little attention from the research community. A healthy placenta is very important to a healthy pregnancy. The ability of the placenta to deliver sufficient oxygen and nutrients to the developing fetus relies on it having a properly developed blood supply network. Several factors are involved in dictating how this blood supply network is developed. We will examine the levels of a group of these factors, called angiogenic factors, in the blood of HIV-positive women during their pregnancy and see if they correlate with the pregnancy outcome. We will compare these factors in both HIV-positive and HIV-negative women to examine if having HIV affects these factors. These experiments may lead to tests that can be performed early in the pregnancy to identify women that are more likely to have pregnancy complications, so more care can be given to them to prevent these complications from occurring.

Most HIV-positive women of child-bearing age receive combination antiretroviral therapy, although very little is known about how each of the antiretrovirals can affect their pregnancy. Using several laboratory tests we will examine if and how different antiretroviral alter the function of trophoblast cells. Trophoblast cells have a key role in the development of the placenta. These experiments will help us understand how antiretrovirals can affect placenta development and may result in more informed treatment choices for HIV-positive women of child-bearing age.

The proposed studies could result in "early warning tests" that could identify HIV-positive women that have a higher risk of developing complications before these complications develop.

Further, the proposed studies could result in a better understanding of the possible effects of antiretrovirals on placenta and fetal development. This will enable HIV-positive women of child-bearing age and their doctors to make better informed choices for their HIV treatment.

Our group is committed to engaging the community in our research. Our research group includes community-based researchers that are community members. We have created a Community Advisory Board, that is co-chaired by two community members, and has a membership that is based on the ethnic and geographic diversity of HIV-positive women in Ontario. We will inform and seek the support of various community groups including Women's Health in Women's Hands and the AIDS committee of Toronto. We plan on involving community members to assist in the development of educational materials and workshops. In addition to publishing our data, we will also circulate our results to the participants of the studies and to the wider HIV community. We believe that only medical practitioners familiar with recent research advancements can provide the best care to their patients. And in order to achieve the higher possible quality of life, people living with HIV and AIDS need to be informed of the latest treatment options.


Title: Malaria and HIV Disease Interactions
Amount: $ 1,483,825
Duration: 1999-2012
Funding Source: CIHR Institute of Infection and Immunity - Operating Grant
Role: Co-Investigator, with Dr. Kevin Kain as Principal Investigator

Abstract: Mounting evidence has demonstrated that two of the most important infectious diseases on the planet, malaria and HIV, negatively affect each other, particularly in the context of pregnancy. Since HIV and malaria are so prevalent, millions of people are co-infected. Even a small deleterious interaction between HIV and malaria would have a massive public health impact. However we know relatively little about the mechanisms underlying these negative disease interactions and how we might effectively intervene. This proposal intends to investigate the basis for the deleterious affect of malaria on HIV and vice versa, so that more effective treatments can be developed and delivered.