Tag Archives: meet the researcher

catherine brissette_meet the researcher

Meet the Researcher: Catherine Brissette, Ph.D.

MEET THE RESEARCHER IS A BLOG SERIES TO INTRODUCE GLA-FUNDED LYME DISEASE RESEARCHERS MAKING A DIFFERENCE IN THE FIGHT AGAINST LYME DISEASE.


#MEETTHERESEARCHER
NAME: Catherine Brissette, Ph.D.
TITLE: Associate Professor, Biomedical Sciences
INSTITUTION: University of North Dakota

Catherine (Cat) Brissette received her B.S. degree in Zoology from Louisiana State University, her M.S. with Dr. Paula Fives-Taylor at the University of Vermont, and her Ph.D. from the University of Washington for her work with Dr. Sheila Lukehart on interactions of oral spirochetes with the gingival epithelium. She continued work with spirochetes as a postdoc with Dr. Brian Stevenson at the University of Kentucky, where she switched to the Lyme disease spirochete Borrelia burgdorferi. Her work with Dr. Stevenson involved studies of outer surface adhesions and regulation of virulence factors. Cat accepted a faculty position at the University of North Dakota in the Department of Microbiology and Immunology (now part of Biomedical Sciences), where she continues her work with pathogenic Borrelia species. Her lab is particularly interested in understanding why B. burgdorferi has a tropism for the central nervous system; that is, why the B.burgdorferi’s surface proteins interact with the hosts’ extracellular matrix, cells, and components of the immune system, and the regulatory mechanisms controlling the expression of these infection-associated proteins.

Dr. Brissette is also a member of GLA’s esteemed Scientific Advisory Board.

Drs. Eva Sapi, Ali Divan, Catherine Brissette, Janakiram Seshu, and Mayla Hsu, GLA’s Director of Research and Science, at GLA’s Lyme Disease Research Symposium 2017

GLA: WHAT MOTIVATED YOU TO FOCUS ON LYME AND TICK-BORNE DISEASE RESEARCH?

CB: My Ph.D. work involved a different kind of spirochete (one involved in periodontal disease); the challenge of working with a different pathogen (the agent of Lyme disease) was exciting.

GLA: WHAT ARE YOU WORKING ON NOW?

CB: We are working on several different aspects of neurological Lyme disease. More specifically, how the bacteria gets into the central nervous system in the first place, how the immune system responds, and how the bacteria adapt to that pressure. We have recently demonstrated that aspects of Bburgdorferi meningeal infections can be modeled in laboratory mice, which opens up a lot of research avenues. In particular, we are interested in the behavioral changes that occur as a result of meningeal infection. For instance, anxiety and memory problems are often reported by Lyme patients, particularly in people with long-term disease or Post-Treatment Lyme Disease Syndrome, and we want to understand how the Lyme disease bacterium and the host immune system contribute to these devastating symptoms. Having a small animal model allows us to more easily test potential treatments and interventions in the lab, prior to testing in people.

GLA: ARE YOU CONFIDENT WE WILL FIND A CURE?

CB: Absolutely. Lyme researchers, like Lyme patients, are tenacious and persistent. We won’t stop.

GLA-FUNDED RESEARCH GRANTS WITH DR. BRISSETTE INCLUDE:

  • “Adverse outcomes in gestation as a consequence of immune responses to B.  burgdorferi infection during pregnancy” (2017-18)
  • “Control of Bb DNA expression” (2016-17)

PUBLICATIONS RE: NEUROBORRELIOSIS

  1. Divan, A., Casselli, T.,Narayanan, S.A., Mukherjee, S., Zawieja, D.C., Watt, J.A., Brissette, C.A., Newell-Rogers, M.K. (2018) Borrelia burgdorferi adhere to blood vessels in the dura mater and are associated with increased meningeal T cells during murine disseminated borreliosis. PLoS One 13(5):e0196893. doi: 10.1371/journal.pone.0196893. PMID: 29723263
  2. Greenmyer, J., Gaultney, R.A., Brissette,A., Watt, J.A. (2018) Primary human microglia are phagocytically active and respond to Borrelia burgdorferi with upregulation of chemokines and cytokines. Front Microbiol. 9:811. doi: 10.3389/fmicb.2018.00811. PMID: 29922241
  3. Casselli, T., Qureshi, H., Peterson, E., Perley, D., Blake, E., Jokinen, B., Abbas, A., Nechaev, S., Watt, J.A., Dhasarathy, A@., Brissette@, C.A. (2017) MicroRNA and mRNA transcriptome profiling in primary human astrocytes infected with Borrelia burgdorferi. PLoS One 12(1):e0170961. doi: 10.1371/journal.pone.0170961. PMID: 28135303 @Co-corresponding authors
  4.  Brissette,A., E.D. Kees, M. Burke, R.A. Gaultney, A.M. Floden, and J.A. Watt (2013) The multifaceted responses of primary human astrocytes and brain microvascular endothelial cells to the Lyme disease spirochete, Borrelia burgdorferi.ASN Neuro 5(3). doi:pii: e00119. PMID: 23883071 Paper highlighted with a podcast: http://www.asnneuro.org/an/005/3/default.htm
  5. Brissette, C.A., H.M. Houdek, A.M. Floden, and T.A. Rosenberger (2012) Acetate supplementation reduces microglia activation and brain interleukin-1beta levels in a rat model of Lyme neuroborreliosis. J Neuroinflammation 9:249. PMID: 23134838

Click here to see GLA’s Research Report, detailing GLA’s research accomplishments

timothy sellati

Meet the Researcher: Timothy J. Sellati, Ph.D.

Meet the Researcher is a blog series to introduce GLA-funded Lyme disease researchers, and in this case, GLA’s Chief Scientific Officer.


 

#Meettheresearcher

NAME: Timothy J. Sellati, Ph.D.
TITLE: Chief Scientific Officer

Dr. Sellati has more than 20 years of Lyme and tick-borne disease research experience. He has published more than 40 peer-reviewed infectious disease papers, nearly 20 of which are focused on Lyme disease. As GLA’s Chief Scientific Officer, he leads GLA’s research initiatives to accelerate the development of more effective methods of diagnosis, the treatment of Lyme and other tick-borne diseases, and the search for a cure. But what makes him tick?

GLA CEO Scott Santarella, GLA grantee Dr. Nicole Baumgarth, GLA CSO Dr. Timothy Sellati
Dr. Sellati, far right, with GLA CEO Scott Santarella and GLA grantee Dr. Nicole Baumgarth at GLA’s Lyme Disease Research Symposium 2018

WHAT MOTIVATED YOU TO FOCUS ON TICK-BORNE DISEASE RESEARCH?

When I began pursuing my Ph.D. from the State University of New York at Stony Brook, I thought I would focus on cancer biology and tumor cell metastasis. Through serendipity I instead found myself training with Martha Furie, Ph.D., a renowned cell biologist, and Jorge Benach, Ph.D., who along with Willy Burgdorfer, Ph.D., discovered that the causative agent of Lyme disease Borrelia burgdorferi  is a bacterial spirochete transmitted by the bite of a black-legged (“deer”) tick.. Although the study of bacteria entering and then escaping from the bloodstream after a tick bite sounds worlds away from studying tumor cell metastasis, there really are some remarkable similarities.

Timothy Sellati
Dr. Sellati served as Distinguished Fellow and Chair of the Department of Infectious Diseases in the Drug Discovery Division at Southern Research Institute

For instance, small cell lung cancers spread via the bloodstream to the liver, lung, bones and brain, but not to other organs that also receive blood. In a similar fashion, B. burgdorferi spirochetes leave the site of inoculation and travel to the joints, heart, and brain, but not to other organs also receiving blood. I wanted to explore and understand why that was so and what controlled where the spirochetes (like cancer cells) could and could not go in the body. I also wanted to determine why certain immune cells responsible for killing and clearing B. burgdorferi instead invade the joint while a different type of immune cell invades the spirochete-infected heart.

WHY DID YOU DECIDE TO MOVE FROM THE LAB TO GLOBAL LYME ALLIANCE?

Dr. Sellati with GLA grantee Dr. Lise Nigrovic at GLA’s Lyme Disease Research Symposium 2018

Joining GLA allows me to make a greater impact, beyond my own academic research program, in helping to solve the mystery of Lyme disease and better understand its impact on patients. I’m most excited about the opportunity to engage scientists and physicians willing to share and learn from one another, willing to approach their work in a cross-disciplinary, inter-departmental and cross-institutional manner and who are willing to alter their notion of “how the world works” when presented with experimental evidence that runs contrary to it. In essence, GLA enables me to serve as scientific ‘cupid,’ supporting young, mid-career, and senior research scientists and physicians who are inclined to “color outside the lines,” challenging conventional thinking and approaches and hopefully getting us to the finish line—preventing future cases of tick-borne illness and curing those individuals already infected.

What drew me to GLA was its reputation. Reviewing its roster of Scientific Advisory Board members, I saw many faces and names with whom I was familiar and had interacted with during my long research career. I was also excited to see the caliber of scientists and physicians whose research the organization had funded in the past or is currently funding.

WHAT IS YOUR VISION FOR GLA’S RESEARCH PROGRAM?

GLA’s goal is to impact patients, and I believe the best way to do that is through research. My strategic vision for GLA is to identify and help direct funds to projects that will drive the development of more accurate and accessible diagnostic tests, treatments for chronic, or persistent, Lyme disease, and a cure. I believe these goals are realistically attainable.

PUBLISHED RESEARCH

(a small sample)

Induction of Interleukin 10 by Borrelia burgdorferi Is Regulated by the Action of CD14-Dependent p38 Mitogen-Activated Protein Kinase and cAMP-Mediated Chromatin Remodeling.

Sahay B, Bashant K, Nelson NLJ, Patsey RL, Gadila SK, Boohaker R, Verma A, Strle K, Sellati TJ.  Infect Immun. 2018 Mar 22;86(4). pii: e00781-17. doi: 10.1128/IAI.00781-17. Print 2018 Apr. 

CD14 signaling restrains chronic inflammation through induction of p38-MAPK/SOCS-dependent tolerance.

Sahay B, Patsey RL, Eggers CH, Salazar JC, Radolf JD, Sellati TJ.  PLoS Pathog. 2009 Dec;5(12):e1000687. doi: 10.1371/journal.ppat.1000687. Epub 2009 Dec 11.

NKT cells prevent chronic joint inflammation after infection with Borrelia burgdorferi.

Tupin E, Benhnia MR, Kinjo Y, Patsey R, Lena CJ, Haller MC, Caimano MJ, Imamura M, Wong CH, Crotty S, Radolf JD, Sellati TJ, Kronenberg M. Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19863-8. doi: 10.1073/pnas.0810519105. Epub 2008 Dec 5.

Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria.

Kinjo Y, Tupin E, Wu D, Fujio M, Garcia-Navarro R, Benhnia MR, Zajonc DM, Ben-Menachem G, Ainge GD, Painter GF, Khurana A, Hoebe K, Behar SM, Beutler B, Wilson IA, Tsuji M, Sellati TJ, Wong CH, Kronenberg M. Nat Immunol. 2006 Sep;7(9):978-86. Epub 2006 Aug 20.

Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products.

Lien E, Sellati TJ, Yoshimura A, Flo TH, Rawadi G, Finberg RW, Carroll JD, Espevik T, Ingalls RR, Radolf JD, Golenbock DT. J Biol Chem. 1999 Nov 19;274(47):33419-25.


LEARN MORE ABOUT GLA’s RESEARCH INITIATIVES AND ACCOMPLISHMENTS: