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Jen-Tsan Ashley Chi:
I was born and grew up in Taiwan. I obtained my MD from National Taiwan University and PhD from Stanford University. From my post-doctoral training with Dr. Patrick Brown at Stanford, I have been using genomic analysis and gene expression to dissect the influences of various tumor microenvironmental stresses in human cancer and tumor heterogeneity. Since arriving at Duke University, we discovered the presence of abundant and diverse species of RNAs in mature erythrocyte, a cell type long thought to lack any DNA or RNA. Since then we have pioneered the efforts to apply the genomic analysis of erythrocyte microRNAs to dissect the phenotypic variations among sickle cell diseases and blood storage. From the investigation of erythrocytes, we have been interested in the role of erythrocyte RNA in the malaria parasites, including the recent adoption of single cell RNA-Seq technology of malaria parasite pioneered by Dr. Katie Walzer during her thesis work in my lab.
Katelyn Walzer:
For over ten years, Dr. Katelyn Walzer has studied the genetics and genomics of multiple apicomplexan parasites, including Toxoplasma gondii, Plasmodium falciparum, and now Cryptosporidium parvum. She completed her PhD in 2018 under the guidance of Dr. Jen-Tsan Ashley Chi at Duke University, where she studied the malaria-causing parasite P. falciparum using high-throughput genomic technologies, including single-cell RNA sequencing. Her work, published in multiple journals including mSphere and PLoS Genetics, identified distinct gene expression differences between male and female parasites during the transmissible sexual stage and uncovered unexpected transcription of genes during multiple times in the P. falciparum life cycle. These findings imply that significant transcriptional diversity allows the P. falciparum parasite to survive its dynamic host environment. Now a post-doctoral fellow in Dr. Boris Striepen's lab at the University of Pennsylvania, Dr. Walzer studies the transcriptional regulators of the C. parvum life cycle and has used single-cell RNA sequencing to determine the genes expressed during the asexual and sexual stages. Further work will focus on functionally characterizing stage-specific regulators and determining single-cell gene expression of the host immune response.
Walzer KA, Fradin H, Emerson LY, Corcoran DL, Chi JT (2019) Latent transcriptional variations of individual Plasmodium falciparum uncovered by single-cell RNA-seq and fluorescence imaging. PLOS Genetics 15(12): e1008506. https://doi.org/10.1371/journal.pgen.1008506
Walzer KA, Kubicki DM, Tang X, Chi JT. Single-Cell Analysis Reveals Distinct Gene Expression and Heterogeneity in Male and Female Plasmodium falciparum Gametocytes. mSphere. 2018;3(2):e00130-18. Published 2018 Apr 11. doi:10.1128/mSphere.00130-18
Researcher Katelyn Walzer and her Ph.D. mentor Dr. Jen-Tsan Ashley Chi used single-cell analysis to study the malaria-causing parasite, Plasmodium. Dr. Walzer is now studying another parasite called Cryptosporidium. In this podcast, they discuss
Jen-Tsan Ashley Chi, MD, PhD, is an associate professor at the Center for Genomic and Computational Biology at Duke University School of Medicine. His former microbiology student, Katelyn Ann Walzer, PhD, is currently working on her post-doc at the University of Pennsylvania with single-cell analysis. They tell listeners about their specific findings on Plasmodium and Dr. Walzer's current focus on Cryptosporidium, a parasite that causes a diarrheal disease, and what else she hopes to study regarding the parasite.
She gives some background on the parasite, describing how detrimental it can be for children in some countries of Africa who've already suffered from other diseases. Cryptosporidium can actually reactivate and cause chronic infection in these children, affecting their general health and quality of life. Dr. Walzer explains how single-cell genomics analysis has allowed her to identify which genes are expressed in the two different matting types (sexual and asexual). Dr. Chi explains how this technique also helped in Plasmodium research because mating is the only way to achieve intrapersonal human transmission, and identifying males and understanding the stages of development in both parasites may offer ways to block their development. Dr. Walzer explains additional findings, plans for upcoming research, and her goals to discover information that will help develop better treatments for infection by Cryptosporidium.
For more information, search these researchers in Google Scholar. Available on Apple Podcasts: apple.co/2Os0myK
Assistant Professor at Icahn School of Medicine at Mount Sinai, Dr. Augusto Rodriguez, talks about the scope of his work and research on different aspects of liver oncology. In this episode, you will learn:
Dr. Rodriguez's work centers around the goal of incorporating molecular information from tumors into tools that can be applied in the clinical setting to improve prognosis predictions, and developing novel methods for early detection of liver cancer. The current gold standard for early detection of liver cancer is a combination of abdominal ultrasonography to look for evidence of small tumor formation, and blood tests to identify the levels of a certain protein known to be elevated in patients with liver cancer.
So, what's wrong with the current gold standard? Dr. Rodriguez explains that in addition to operator error with regard to the ultrasound procedure, it requires patients to travel to an imaging center every six months, which is difficult to manage for many people. Due to the inconvenience and difficulty presented by compliance with the gold standard protocol, many people end up developing liver cancer that goes undetected for far too long.
A potential solution that Dr. Rodriguez has his eyes on is a technology called liquid biopsy. In essence, it entails an analysis of tumor components within the bloodstream, such as fragments of DNA from tumors or extracellular vesicles released from tumors. The detection of such components in a blood sample taken at the point of care can detect liver tumors when they are very small, leading to better overall prognosis. In addition, liquid biopsy may address another complication in the area of liver cancer treatment, which is the determination of how best to sequence the many therapies that have become available in recent years.
Dr. Rodriguez discusses a number of fascinating topics. Tune in for all the details. Available on Apple Podcasts: apple.co/2Os0myK
Dr. Ray Kaplan is a professor in the Department of Infectious Diseases at University of Georgia. He joins the show to discuss the details of his research on parasitism and drug-resistant parasites. Tune in to discover:
Dr. Kaplan's interest in parasites was sparked after he found himself working in a parasitology lab as an undergraduate at Virginia Tech. He continued conducting research on parasitology while in veterinary school, and eventually entered academia to become a professor and focus more exclusively on his research. He studies primarily parasites of livestock and dogs, and aims to better understand and solve the problems posed by increasing numbers of drug-resistant parasites.
Dr. Kaplan discusses the life cycle of common parasites in dogs, what happens when a human being is infected by hookworms, the coevolution of the gut microbiome and intestinal worms, evidence which suggests that some parasites may be critical to the human immune response and protection against autoimmune diseases, what mechanisms are used by parasites that enable them to complete their life cycles, challenges and roadblocks to progress in parasitology, drug resistance of roundworms infecting turkeys, and so much more.
For information on these and related topics, check out the following:
https://vet.uga.edu/person/ray_m-_kaplan/
https://www.wormx.info/ Available on Apple Podcasts: apple.co/2Os0myK
Professor Robert Poulin's interests center around how and in what ways parasites manipulate the behavior of their hosts. He joins the show to discuss his fascinating research. In this episode, you will learn:
Over the course of millions of years, parasitism has been gradually shaped and enhanced by evolution, resulting in parasites that have the amazing ability to induce behavioral and physical modifications in their hosts in ways that ultimately benefit the parasite. Consider, for instance, the hairworm, which is a parasite that grows inside a terrestrial insect in coil-like fashion until it becomes two to three feet in length, at which point it induces the insect to essentially commit suicide for its survival; the hairworm causes the insect to search for and jump into a body of water, where the hairworm can then emerge from the parasite (killing it in the process), find a mate, and reproduce.
This is just one example of a parasitic relationship that Poulin hopes to better understand. In part, his research involves an examination of gene expression within the genome of the brain cells of infected host insects. Poulin is also interested in other mechanisms by which parasites manipulate hosts, such as those that may involve the microbes that parasites carry with them, or the presence of symbiotic viruses that manipulate host behavior. Among other topics, Poulin discusses how parasites are so effective at evading host immune systems, counter-adaptations to host defenses, examples of how parasites can form part of a larger ecosystem, which tissues are preferential for parasites to reside in and why, and so much more.
Tune in for all the details and learn more about Poulin's research by visiting https://www.otago.ac.nz/parasitegroup/home.html. Available on Apple Podcasts: apple.co/2Os0myK
Ponni Perumalswami treats patients who have advanced liver diseases. She also is working to reach communities at risk for viral hepatitis B and C to connect them to testing, education, and healthcare. She explains
Ponni Perumalswami is an associate professor of medicine in the Division of Liver Diseases at Mt. Sinai School of Medicine. She tells listeners that there's an at-risk population for hepatitis B and C that she and her colleagues are targeting. In the U.S., while the diseases are less common in the general population, at-risk groups who immigrate from areas with higher rates, specifically Asian and African-born communities, are hard to reach. Because they may not have insurance and are not English speakers, they aren't in touch with primary care doctors who might normally screen for these diseases and they can be asymptomatic for years. Her outreach efforts include testing within the communities and awareness-raising efforts.
Dr. Perumalswami explains how these diseases work. She explains that hepatitis B is a DNA virus that largely infects foreign-born populations because the U.S. has had the means to vaccinate and test for this disease. It spreads by a vertical transmission from mother to child. Hepatitis C is transmitted through blood exposures, so through intravenous drug use, blood transfusions, and organ donations done before 1992 when testing became available. Even though each can exist in the body silently for years, they can still do tremendous damage in the liver, and increase one's risk for cirrhosis, cancer, and other disease of the liver that may need liver transplantation.
For more, see the Mt. Sinai Liver Diseases Division website https://www.mountsinai.org/care/liver-diseases/research Available on Apple Podcasts: apple.co/2Os0myK
Professor Nicolas Vabret has had an almost lifelong interest in viruses, and has been studying them since obtaining his PhD in 2011. He joins the show to discuss a number of interesting topics, including the following:
What happens as soon as a virus enters the body? What allows the body to recognize non-self cells and to respond accordingly? Some cells have the ability to detect the presence of viruses and bacteria that enter the body, and activate the first step in the innate immune response, which eventually leads to the activation of the second phase of the immune response. Vabret is particularly interested in understanding the early molecular mechanisms that make this possible.
He describes the differences between the innate immune response and adaptive immune response, the role and function of pattern recognition receptors, RNA production, the importance of cytokines in the response to virally-infected hosts—in particular those infected with COVID-19, viral strategies for counteracting immune responses, characteristics of the HIV virus and chimpanzee versus human immune responses to it, current research in the field of immunology, and so much more. Available on Apple Podcasts: apple.co/2Os0myK
Vivek Mutalik is a synthetic biologist who studies biochemical energy and uses tools to understand how bacteria survive in their environment. He's currently focused on bacteriophages. He discusses
Vivek Mutalik is a research scientist at Lawrence Berkeley National Laboratory in the Environmental Genomics and Systems Biology Division as well as the Biological Systems and Engineering Division. He works with two key questions: how do phages and bacteria interact and how can scientists engineer phages. The goals connecting these foundational and engineering aspects include using phages for microbiome work and for eliminating pathogens. He explains his work studying the genes and mechanistics of bacteriophages by first giving an overview of the vast diversity and huge number of phages. He remarks that scientists know that they are virtually everywhere on earth, yet hardly know anything about their impact.
He explains that there are different types of phages, some that infect specific bacteria and some that are broad spectrum, able to target lots of different bacteria. He says that while we don't understand how this specificity happens and what their design rule is—the key of phage biology—his research hopes to change this and better understand the engineering of these phages. His research studies the phages' genes to understand which genes encode which function. He explains some techniques and findings in more detail and says we need to understand this foundation to manipulate the microbiome so practitioners can get rid of specific microbes, not healthy ones, with precision.
To find out more, find him on twitter as @vivek_mutalik and see his lab web site: biosciences.lbl.gov/profiles/vivek-mutalik/ Available on Apple Podcasts: apple.co/2Os0myK
As a research fellow in clinical medicine, Sharee Basdeo focuses primarily on tuberculosis (TB), which has co-evolved with the human immune system for thousands of years. By tuning in, you'll discover:
There are roughly three categories of responses to TB: a person can be exposed to TB but mount no immune response and show no signs of having been exposed, a person can be exposed and their immune system can mount an effective response which contains the TB infection and puts it in a dormant state, or a person can be exposed and develop active TB disease.
So, what determines which course of action will occur? This is a question that has yet to be answered, and one that many people are actively researching. Basdeo discusses this topic, along with many other fascinating subjects, including how those who harbor latent TB can develop active TB as they age, innate immunity, what happens when the wrong drug or wrong dose of drug is taken for TB, how the lung and gut microbiome might be related to the immune response for TB, the mutagenesis of TB and why it is difficult to kill TB, how TB finds ways to tune down the immune response to allow itself to exist undetected, and the importance of Th17 cells.
Visit https://www.tcd.ie/research/profiles/?profile=sbasdeo to learn more about Basdeo's work. Available on Apple Podcasts: apple.co/2Os0myK
Filipe Cabrerio researches how a host's microbiome and physiology interact in the context of different conditions such as aging and metabolic syndrome while taking various medications. He shares some his lab's research with listeners, explaining
Filipe Cabreiro holds a Sir Henry Dale Fellowship in the London Institute of Medical Sciences at the Imperial College of London. His lab works to understand how the microbiome interacts with a host's physiology—how the microbes that one produces interact with others, especially when both are challenged by daily medications taken to deal with disease and in the conditions of aging. The lab recently made an important discovery in the context of cancer drugs: they found that classic drugs for colorectal cancer were modified by microbial metabolism that reduced or amplified the action of the drugs. Further, they found that certain components of food could change that response.
He also discusses a study on metformin, a drug taken for type 2 diabetes, and its interaction with the microbiome. They found that nutrients, the host's microbiome, and the drug interact in an important way. Metformin makes selective pressures on certain gut microbes, which translates into longer lasting change associated with positive effects. They think metformin pushes for certain conditions that allow some healthful microbes to survive and also pushes strong metabolic change. The consequences of that change is the production of molecules such as fatty acids and others that can actively regulate the host's physiology and metabolism. He explains the nature of this interaction and the significance in more detail along with challenges to these kinds of studies, further hypotheses, and future research he hopes to take on.
For more, see his lab's web page: cabreirolab.org. Available on Apple Podcasts: apple.co/2Os0myK
Professor Clive Shiff is an entomologist who shares fascinating insight into his work. Tune in to discover:
For two years, Shiff lived in the African bush, where he encountered elephants, rhinoceros, leopards, hippopotamuses, and many other animals face-to-face. He shares his experiences, what he learned during this time, and what he did to avoid deadly parasites and diseases like malaria and sleeping sickness.
Shiff discusses the efforts to eradicate malaria in the 1950s, parasitic diseases such as sleeping sickness and schistosomiasis, what therapies and sanitations efforts have been implemented in response to schistosomiasis and why it has been so difficult to combat, and how he is trying to improve diagnostics for parasitic diseases. Available on Apple Podcasts: apple.co/2Os0myK
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