Serve Lab

A Research Program Focused on Immunotoxicology and Cell Biology

Idaho State University

https://www.isu.edu/biology/people/faculty---professors/kinta-serve/

Introduction

Lab Projects

Project 1: Examining Immune Responses to Asbestos

Project 2: Examining the Role of Plasminogen in Pleural Fibrosis

Project 3: Antibody Screening

Project 4: Post-translational Modifications of Plasminogen

Lab People

Vertically Integrated Projects (VIP)

Work Hard, Play Hard!

Introduction

In the Serve lab, we focus on cellular responses to environmental toxins like asbestos. We are interested in how exposures affect cells locally (at the site of exposure) and systemically (immune cells) to drive diseases like pleural fibrosis and autoimmunity. We use a variety of molecular techniques, cellular and animal models, and immunology methods to answer these big research questions.

If you want to find out more about ISU degree programs, check out this site: https://www.isu.edu/biology/degree-programs/

If you are a current ISU undergrad interested in research opportunities, email me at servkint@isu.edu

Dr. Kinta M. ServeAssociate Professor of Biology

Publications on PubMed

Cultured macrophage cells engulfing amphibole asbestos fibers.

Amphibole Fibers

What is Asbestos and how are we exposed?

Asbestos are naturally occurring, silicate mineral fibers that are classified based on their shape: amphibole are straight-chained while chrysotile are curly, or serpentine. Inhalation of these fibers results in many diseases, most notable of which is mesothelioma, or cancer arising in the mesothelium. Mesothelioma is a very aggressive and deadly cancer and is almost exclusively caused by asbestos exposure. However, fiber exposures can cause other diseases as well, including lung cancer, GI-tract cancers, interstitial fibrosis, and pleural disease (effusions, adhesions, and fibrosis). Often these diseases arise decades after asbestos exposures.

The term "asbestos" refers only to six regulated fibers, but we know that many "asbestiform-like fibers" also cause disease in a manner similar to asbestos fibers. They can also cause immune dysfunction and have been associated with development of systemic autoimmune diseases in some populations, as has been noted following exposures in and around Libby, MT during the 20th century. https://scholarworks.montana.edu/xmlui/bitstream/handle/1/15270/Pfau_JTEHptA_2018_FINAL.pdf;jsessionid=DDE4BB00833C9CD90489E0CE1F212DFD?sequence=1

Asbestos exposures are classified as occupational or environmental, depending on the source of the fibers. Chrysotile fibers were used in commercial products for many decades due to their high tensile strength and heat-resistant properties. Asbestos-contaminated products are still around today; for example, houses built prior to 1940 likely used asbestos in the construction materials and exposures can still occur if those materials are disturbed. The use of asbestos in commercial products has decreased dramatically since the 1970s, but use of asbestos is not completely banned. Additionally, asbestos is still mined and used world-wide, thus occupational exposures still occur. Of growing interest are environmental exposures, which occur when natural asbestos outcroppings are disturbed, often due to construction, off-road recreation, dust storms, or erosion. Inhalation of these fibers are associated with asbestos-related diseases and exposures may become more common due to climate change and resulting droughts, fires, floods, and dust storms.

Lab Projects

Asbestos exposure triggers inflammation at the sites of fiber deposition. Since asbestos fibers cannot be easily degraded by the immune system, they are biopersistant, leading to on-going inflammation and cellular responses. We hypothesize that this early, non-resolving inflammation drives later disease development. Therefore, our research focuses on:

Understanding the cellular responses to asbestos fibers, especially mesothelial and macrophage cells
Examining how inflammation is related to disease development, especially fibrosis and autoimmunity
Understanding how post-translational modification (PTM) of native proteins can serve as neo-antigens for the immune system

Project 1: Examining Immune Responses to Asbestos

Inflammation is a hallmark of asbestos-associated diseases and common following exposure to many inhaled toxicants. Following initial inflammation and removal of insults from the body (i.e., asbestos, pathogens, etc.) immune resolution begins. This resolution stage is associated with tissue repair, decreased immune responses, and a return to homeostasis. However, if inflammation is prolonged or resolution does not occur, chronic diseases can develop.

In our models of low-dose asbestos exposure, we have noted an on-going inflammatory response within the pleural cavity but not in the lungs, suggesting differential responses to fibers in these two sites. We suspect that the pleural cells are more sensitive to asbestos insult and that persistent inflammatory responses in this cavity perpetuate asbestos-associated diseases, like pleural fibrosis or mesothelioma. We are currently studying the kinetics of acute inflammatory responses following asbestos exposures. Read more about this project, and the INBRE pilot award supporting this work, here: https://www.isu.edu/news/2023-spring/inbre-grants-fund-asbestos-exposure-treatment-embryo-development-research-at-idaho-state-university.html

Diagram of the movement of inhaled asbestos fibers from the lung into the pleural cavity. Fibers may accumulate in the pleura or move via the lymphatics and accumulate in extra-pulmonary sites. Picture credit: Saige Rigby. Originally published Oct,. 2024 in Asbestos disease pathogenesis: The long and short of it. https://www.openaccessgovernment.org/article/asbestos-disease-pathogenesis-the-long-and-short-of-it/182029/

Project 2: Examining the Role of Plasminogen in Pleural Fibrosis

Plasminogen (PLG) is a protein secreted by the liver and activated to plasmin on various cell surfaces. Plasmin is a serine protease that aids in extracellular matrix degradation. ECM degradation can assist in cell migration and tissue repair. We recently showed that Plg can bind to mesothelial cell surfaces via multiple receptors and be activated to plasmin. PLG activity increases mesothelial cell migration and collagen cleavage, possibly promoting wound healing activities in mesothelial cells or metastasis in mesothelioma cells. Read more here: https://www.mdpi.com/1422-0067/23/11/5984

We have also shown that asbestos exposure results in antibodies that block PLG activation on mesothelial cell surfaces, which leads to collagen accumulation. We are now examining the mechanisms by which PLG binding may reduce collagen accumulation and anti-PLG antibodies may contribute to fibrosis, or excess collagen deposition. Read more here: https://www.tandfonline.com/doi/abs/10.3109/08958378.2013.848249 https://journals.physiology.org/doi/full/10.1152/ajplung.00462.2015

Histogram showing expression of Plg receptor Enolase-1 (stained with APC) on the surface of mesothelial cells.

Project 3: Antibody Screening

As part of an on-going effort to identify patients with asbestos-associated autoantibodies, we work with the Libby Center for Asbestos Related Disease clinic and researchers from Icahn School of Medicine at Mt Sinai to screen patient sera. The goal is to identify patients with asbestos-related diseases and monitor disease progression to better understand the antibody-disease correlations.

We have screened over 700 patient serum samples for asbestos-associated antibodies, including mesothelial cell autoantibodies and anti-plasminogen antibodies. We have shown the overall prevalence of anti-plasminogen antibodies to by 15% in the screened population. Interestingly, antibody prevalence is slightly higher in male than female patients, even though the majority of patients are exposed via environmental and not occupational routes. For many autoimmune diseases, prevalence is significantly higher in females than males, suggesting different mechanisms may drive asbestos-associated responses.

Project 4: Post-translational Modifications of Plasminogen

Citrullination is a type of post-translational modification that changes the amino acid arginine to the non-coded residue citrulline. Citrullination of proteins has been shown in several systemic autoimmune diseases and we recently discovered that the protein plasminogen can be citrullinated. Our current projects are focused on examining the expression of citrullinating enzymes (peptidyl arginine deiminases) after asbestos exposure, identifying the lung protein targets of citrullination, and determining the contribution of citrullination to the formation of autoantibodies, like anti-plasminogen.

Figure: Exposure to LA increases lung citrullination in C57/Bl6 mice exposed to vehicle control (A) or amphibole asbestos (B). Lungs collected 21 days after exposure were paraffin embedded and prepared for imaging. Citrullination was detected using an anti-citrulline-Rhodamine antibody followed by imaging on an Olympus FV1000 confocal microscope (A & B).

Joselynn Castillo, INBRE Fellow 2020

Lab People

We are constantly looking for excellent people to join the lab. If you are excited about cell biology or toxicology and want research experience, you are welcome here!

Undergraduate student opportunities include: volunteering, earning credit, working as a CPI or INBRE fellow.

Graduate student opportunities include BS/MS dual degree, MS in Biology or Microbiology, Ph.D. in Biology or Microbiology, or DA in Biology

Magdalena Alba

Reagan Badger, B.S./M.S. in Biology, 2021

Larisa McOmber and Natalie Empey at the Idaho Conference on Undergraduate Education, Boise ID, 2024

Society of Toxicology Meeting, 2016, Baltimore MD.

Left to right: Kinta Serve, Avery Salmon, Michael McLawhorn

Zach Ditzig, MS in Microbiology, 2021

Current Lab Members

Graduate students
- Larisa McOmber, Accelerated MS student
Undergraduate students
- Saige Rigby
- Natalie Empey
- Darious Salas
- Trenton Shappee

Some Past Lab Members and their Current positions

Zach Ditzig, M.S. in Microbiology- research assistant
Reagan Badger, B.S./M.S. in Biology- in medical school at University of Washington, WWAMI program
Ujjwal Adhikari, M.S. in Microbiology- research assistant
Dillon Stevens- in medical school at University of Utah
Sebastian Madrigal Nunez- in medical school at UCLA
Jesse Salas- accepted to PA school at ISU
Joselynn Castillo -in dental school at ISU/Creighton University
Michael McLawhorn, M.D.
Avery Salmon, MS in Therapeutics and Pharmacology

Vertically Integrated Projects (VIP)

VIP courses offered at Idaho State University enable undergraduates at all stages to earn credits while gaining valuable research skills. The Immunotoxicology VIP course is run by Dr. Serve and focuses on understanding the molecular mechanisms underlying autoimmune disease development.

Skills that students learn in the Immunotoxicology VIP include: pipetting, histology, ELISA, immunoblots, microscopy, and more!

Learn more here: https://www.isu.edu/biology/departmental-resources/cre/vip/