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Ignacio Mata Laboratory

❮Genomic Medicine Ignacio Mata Laboratory
  • Ignacio Mata Laboratory
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Principal Investigator

Ignacio Mata Headshot

Ignacio Mata, PhD

Assistant Staff
Email: matai@ccf.org
Location: Cleveland Clinic Main Campus

Research

Every person inherits information (genes) from their parents that determines characteristics like height, eye and hair color or skin tone. But these genes also carry information that can protect or increase our chances of developing certain diseases. Dr. Mata's lab is working toward identifying and understanding the genes that play a role in those diseases that affect the brain (neurological disorders). These include the very well-known Parkinson’s disease (PD), but also other, less common, disorders, such as a form of PD that presents with severe cognitive problems/dementia (PDD) and another type of dementia called Dementia with Lewy Bodies (DLB). Identifying these genes is very important as they represent candidates for novel therapies that can help treat these disorders.

Dr. Mata's lab tries to include patients from all ethnicities in its studies, and is privileged to coordinate the Latin American Research consortium on the Genetics of PD (LARGE-PD). This consortium is trying to understand if these genetic factors are the same between populations or specific to certain populations. This inclusion of patients from all genetic backgrounds will be a key factor in developing genetic-based, personalized treatments.

Learn more on the Research tab.


Biography

Ignacio Fernandez “Nacho” Mata, PhD, is the principal investigator of the Mata Lab. He studied biology at the Universidad de Oviedo in Spain, where he later obtained a PhD in neurogenetics. He has been researching the genetics of neurological disorders, especially Parkinson’s Disease, since 2001. He has been very fortunate to have trained with some of the best in the field at the Mayo Clinic, the University of Washington, and the VA Puget Sound. In 2006, Nacho was invited to a meeting by SOLAMA, the Latin American movement disorder society, in Lima, Peru. There he had the opportunity to meet some incredible movement disorder specialists from several Latin American countries who were very eager to have access to genetic testing for their patients. Nacho offered to help, and LARGE-PD was born. He began working at the Cleveland Clinic in September of 2018. Nacho hopes to do everything possible to advance the field of Parkinson’s disease, which will help to provide better care for patients and hopefully be able to slow or stop the disease all together someday soon. In LARGE-PD, his motivation is to ensure that these advances apply to everyone, regardless of their ethnicity or country of origin. He wants to assist in building the necessary resources, both physical and in terms of personnel, to allow scientists in Latin America to perform high-quality research locally. Finally, Nacho would like to educate clinicians, researchers, and most importantly patients about genetics research and the importance of their participation, ensuring that these populations are not left behind. Outside the lab, Nacho enjoys traveling, biking, hiking, camping, and spending time with family.


Education & Professional Highlights

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Research

Research

Overview

It is a very exciting time to be in the field of human genetics. Since the sequencing of the human genome in 2003, genetics have tremendously improved the understanding of many human diseases, as well as nominated new targets for future therapies.

Dr. Ignacio Mata and lab members posing for a picture in their lab.

Dr. Mata and lab members.

Dr. Mata's primary research goals are directed toward understanding the genetic component of neurological disorders, in particular Parkinson’s disease (PD), Parkinson’s Disease Dementia (PDD) and Dementia with Lewy Bodies (DLB). Most neurological disorders are very complex, both clinically and genetically, thus proposing a very interesting challenge. In most cases they are the result of a complex interaction between one’s genetics and the environment. Dr. Mata's lab uses approaches like case-control and family studies to identify those genetic risk factors that modify risk or cause the disease.

A significant focus of Dr. Mata's research has also been performing genetic studies in non-European populations, especially those with a minority ethnic background such as Latinos. For this Dr. Mata created and coordinated the Latin American Research consortium on the Genetics of PD (LARGE-PD), a collaboration of more than 37 institutions across many countries in Latin America. The reason behind it is that there is a tremendous lack of diversity in genetic research, with most large-genetic studies including only people of European ancestry, despite the fact that most diseases affect people from all genetic backgrounds. This is increasing the already existing health disparities in these populations.

Our lab and study aims include:

  • Identifying unique genetic and environmental exposure factors that may impact Hispanic populations and their risk of developing PD, as well as disease severity.
  • Leveraging Cleveland Clinic’s large patient population and mass electronic health record data with genetic data from patient samples to create predictive PD severity and progression models using machine learning.
  • Creating a novel questionnaire in order to address gender-based disparities in genetic and PD research, and using women’s health factor data in severity prediction models.
  • Extending these models and aims to other neurological disorders and patient populations.
  • Creating a patient registry, database, and biorepository as a “one stop shop” for PD research at Cleveland Clinic.
  • Applying these results to improve patient treatment and outcomes for these neurological disorders.

 

Current Projects

Latin American Research Consortium on the Genetics of Parkinsons Disease (LARGE-PD) USA
Our U.S. cohort has been approved and is actively recruiting through Cleveland Clinic, the Genomic Medicine Institute and other associated organizations. Our goal is to learn more about the genetic risk factors that play a role in the development of parkinson's disease (PD) in Latinos. The entire recruitment process is conducted remotely, with the consenting process done by phone, questionnaires distributed online and by email, and saliva samples collected by mail. Saliva collection kits are mailed to participants with additional study materials at no cost to the participant. Learn more about LARGE-PD.

Constructing a Prediction Tool for Severity in Women with Parkinson’s Disease
Parkinson’s disease (PD) is the second fastest growing neurodegenerative disorder worldwide, with an estimated 13 million people being diagnosed by 2040. For PD, men are almost two times more likely to get it than women, however, women experience a faster progression and lower survival rate. Women also tend to be diagnosed much later, long after symptoms are present. There is little being done in clinical care or research to address the stark differences observed between sexes. The current questionnaires being used in PD research and clinical care are gender-neutral or only focus on hormone replacement therapy. The goal of this study is to deploy our novel women’s health questionnaire to all women with PD being seen at Cleveland Clinic, LARGE-PD, PDGENEration within and throughout the Americas to elucidate the role of women-specific health factors alongside other factors in the severity and progression of PD. This involves building multivariate predictive health models via machine learning.

Genetic-Based Precision Medicine in Migraine Treatment
Migraine is a highly heritable complex brain disorder that impacts approximately a billion people worldwide. A novel preventative treatment for migraines are calcitonin gene-related peptide (CGRP) inhibiting monoclonal antibodies (MABs). The goal of this project is to understand the clinical, demographic, and quality of life factors that correlate with CGRP MABs treatment outcomes (defined as reduction in migraine frequency), and assess if a model including genetics can help predict those outcomes. We will do this by developing stepwise multivariable logistic regression models with and without genetic data from patient saliva/blood samples. Multivariate predictive health models will also be built via machine learning.This project is funded by a one year, $100,000 research co-laboratories award from Cleveland Clinic.

Cleveland Clinic Comprehensive Parkinsonian Disorders Registry, Biorepository and Database
The purpose of this registry is three-fold:

  1. To compile a list of patients with Parkinsonian disorders being seen Cleveland Clinic and other partner organizations interested in participating in current and future research. This will provide researchers with a list of interested candidates, and necessary information about their symptoms.
  2. To collect and store human biological samples (e.g. biofluids) from Parkinson’s patients, their family members, and healthy controls receiving care at Cleveland Clinic and partner institutions. An environmental exposures questionnaire will be an option for these patients.
  3. To establish a database of genetic, clinical, demographic, environmental, and women’s health data associated with Cleveland Clinic and partner organization patients diagnosed with a Parkinsonian disorder.

This will allow our team, and other IRB approved research teams to view, analyze, and create clinical studies from this de-identified aggregated PD data. It will also allow us to learn more about the many risk factors that play a role in the development, progression, and outcomes of Parkinson’s disease. We are collecting environmental exposure, and other life event data, that may allow Cleveland Clinic teams to determine if specific factors are also implicated in the development and/or progression of PD, and how those life events interact with the genetic factors identified in our cohort. This will allow our team to create multivariable predictive models of PD progression that may help future clinical and research efforts in treating PD through additional sub-studies.

Cleveland Clinic Latino Epidemiology Cohort
Cleveland Clinic researchers Stephanie Schmit, PhD, MPH, and Ignacio Mata, PhD, from the Genomic Medicine Institute are establishing the Cleveland Clinic Latino Epidemiology (CCLE) Cohort. The aim is to recruit Latino patients from Cleveland Clinic’s Ohio and Florida locations to build the initial CCLE Cohort. The CCLE Cohort will be utilized to study the biological causes for disease risk and outcomes. The initial focus will be on Parkinson’s disease and colorectal cancer. The CCLE Cohort will serve as a resource for additional Cleveland Clinic locations, and its leaders hope it can be harnessed to investigate other disorders in Latino populations. The CCLE Cohort will leverage Cleveland Clinic’s large patient volumes and sophisticated electronic health record to build a research infrastructure that additional institutes and locations will be able to access when conducting health disparities research in the future.This project is funded by a one year, $100,000 research co-laboratories award from Cleveland Clinic. Learn more.

Media

Blog: Increasing Underrepresented Hispanic Participation in Parkinson’s and Genomic Research Through the LARGE-PD Study | GP2.org | September 27, 2021

Our Team

Our Team

Henry Mauricio Chapparo

Graduate Student
chapparoh@ccf.org

Diana Cubas

Research Scholar
cubasmd@ccf.org

Nicolas Gutierrez

Research Coordinator
gutiern@ccf.org

Read Bio

Nicolas Gutierrez is a Research Coordinator II for the Mata Lab. He received a bachelor’s degree from Johns Hopkins University, where he studied neuroscience and psychology. Nicolas has worked in several research laboratories prior to arriving in the Mata lab, with a focus on neuroscience-oriented labs. He started working at the Cleveland Clinic in 2019 as a research coordinator in the department of Physical Medicine and Rehabilitation. He joined the Mata team in order to further pursue research on Parkinson’s disease, and to contribute to LARGE-PD’s mission to work with Hispanic communities. Nicolas is incredibly interested in neurodegenerative diseases and their pathophysiology, genetics, and treatment.

Miguel Inca Martinez

Senior Research Technologist
incam@ccf.org

masone5@ccf.org

Seysha Mehta

Research Assistant
mehtas4@ccf.org

Read Bio

Seysha Mehta joined the Mata Lab as a Research Assistant in July 2021 on a gap year with plans to attend medical school. She graduated from Dartmouth College with a double major in Biology and Psychology and a minor in Hispanic Studies. Some of Seysha’s previous research experience at the Cleveland Clinic includes exploring the possibility of using digital data to standardize the NYHA classification of heart failure patients under Dr. Jim Young and investigating how to personalize photodynamic therapy in treating basal cell carcinoma under Dr. Edward Maytin. She believes that the blend of backgrounds, ethnicity, heritage, culture, sexual orientation, and gender make the human species vibrant, interesting, and beautiful.

Thiago Peixoto Leal, PhD

Postdoctoral Fellow
peixott@ccf.org

Read Bio

Thiago Peixoto began working as a postdoctoral researcher at the Mata Lab in April of 2021. He has a bachelor's degree in computer science from the Universidade Federal de São João Del Rey and a master's and PhD in Bioinformatics from the Universidade Federal de Minas Gerais, both of which are in Brazil. He previously spent nearly ten years working at the Human Genetic Diversity Laboratory with one of the greatest population geneticists in Brazil. They made many great achievements in the studies of Latin Americans, including mapping the admixture of Brazilian populations and inferring their admixture dynamics. They also investigated Native American populations in Peru, as well as how different African groups contributed to the formation of American populations during the African Diaspora.

Janvi Ramchandra

Research Scholar
ramchanj@ccf.org

Shilpa Rao

Graduate Student
raos3@ccf.org

Read Bio

Shilpa Rao is a Molecular Medicine PhD student at the Cleveland Clinic. She has a degree in molecular biology from Loyola University Chicago and became involved with LARGE-PD after listening to a presentation from the Mata Lab for her PhD program. She was immediately intrigued and wanted to become involved in the initiative. Shilpa strongly believes that diversity is a necessity. In society, the need to accept and represent all people is acknowledged, but it can be overlooked in the science community. With the growth of genetic research, it is astonishing that so much of the representation has been from people of European ancestry.

Publications

Selected Publications

View publications for Ignacio Mata, PhD
(Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)


Key Publications: (from newer to older)

Characterizing the Genetic Architecture of Parkinson's Disease in Latinos

Loesch DP, Horimoto ARVR, Heilbron K, Sarihan EI, Inca-Martinez M, Mason E, Cornejo-Olivas M, Torres L, Mazzetti P, Cosentino C, Sarapura-Castro E, Rivera-Valdivia A, Medina AC, Dieguez E, Raggio V, Lescano A, Tumas V, Borges V, Ferraz HB, Rieder CR, Schumacher-Schuh A, Santos-Lobato BL, Velez-Pardo C, Jimenez-Del-Rio M, Lopera F, Moreno S, Chana-Cuevas P, Fernandez W, Arboleda G, Arboleda H, Arboleda-Bustos CE, Yearout D, Zabetian CP, 23andMe Research Team, Cannon P, Thornton TA, O'Connor T D, Mata IFǂ, and Latin American Research Consortium on the Genetics of Parkinson's, Disease (2021) Characterizing the Genetic Architecture of Parkinson's Disease in Latinos. Ann Neurol. 90(3):353-365. doi: 10.1002/ana.26153. PMID: 34227697

No Previous Genome-Wide Association Study (GWAS) included Latino individual. We used the LARGE-PD cohort to perform the first GWAS in this population. We showed that a variant in the SNCA gene, rs356182, achieved genome-wide significance in both the discovery and the replication cohorts including 23andMe. We also identified an association with a novel gen, NRROS, although we were not able to validate this result. Taking advantage of the high admixture present in our cohort we performed admixture mapping analysis and identified a locus on chromosome 14, containing the gene STXBP6, which achieved significance especially in those of Native American ancestry. A second locus on chromosome 6, containing the gene RPS6KA2, achieved significance in those with African ancestry. Thus our study demonstrated the importance of the SNCA locus for the etiology of PD in Latinos and nominated a novel population specific association in the NRROS gene. By leveraging the demographic history of our cohort via admixture mapping, we identified two potential PD risk loci that merit further study.


Polygenic risk prediction and SNCA haplotype analysis in a Latino Parkinson's disease cohort, Parkinsonism Related Disorders

Loesch D, Horimoto ARVR, Sarihan EI, Inca-Martinez M, Mason E, Cornejo-Olivas M, Torres L, Mazzetti P,  Cosentino C, Sarapura-Castro E, Rivera-Valdivia A, Medina AC, Dieguez E, Raggio V, Lescano A, Tumas V, Borges V, Ferraz HB, Rieder CR, Schumacher-Schuh A, Santos-Lobato BL, Velez-Pardo C, Jimenez-Del-Rio M, Lopera F,  Moreno S, Chana-Cuevas P, Fernandez W, Arboleda G, Arboleda H, Arboleda-Bustos CE, Yearout D, Zabetian CP, Thornton TA, Mata IFǂ,  O'Connor TDǂ.  Polygenic risk prediction and SNCA haplotype analysis in a Latino Parkinson's disease cohort, Parkinsonism Related Disorders.102:7-15

Statistical models have suggested that there is a lost of accuracy when using data coming only from European individuals to predict disease risk using Poligenic Risk Scores (PRS). We used the LARGE-PD GWAS data to test whether or not this is true in Parkinson’s Disease. We used the largest European GWAS from Nalls and colleagues to build a PRS and see the accuracy to separate cases and controls in Latinos. Surprisingly the predictive performance of the PD PRS was remarkable showing an area under the receiver-operator curve (AUC) of 0.668, higher than for Europeans. Interestingly this was mostly due to the variant rs356182 at the SNCA locus which explained the largest proportion of trait variance out of the variants included in the GWAS-significant PD PRS. Further haplotype analysis showed that although this variant is in Europeans, the European and the Latino haplotypes only share 14% of the variants, thus pointing to this SNCA variant as the probable cause for the association. Our study concluded that the PD PRS has potential for PD risk prediction in Latinos, but variability caused by admixture patterns and bias in a European-ancestry PD PRS data limits its utility. The inclusion of diverse subjects can help elucidate PD risk loci and improve risk prediction in non-European cohorts.


Underrepresented Populations in Parkinson's Genetics Research: Current Landscape and Future Directions

Schumacher-Schuh A F, Bieger A, Okunoye O, Mok K Y, Lim S Y, Bardien S, Ahmad-Annuar A, Santos-Lobato B L, Strelow M Z, Salama M, Rao S C, Zewde Y Z, Dindayal S, Azar J, Prashanth L K, Rajan R, Noyce A J, Okubadejo N, Rizig M, Lesage S, Mata I Fǂ, and Global Parkinson's Genetics Program. Underrepresented Populations in Parkinson's Genetics Research: Current Landscape and Future Directions. Mov Disord  (epub). http://dx.doi.org/10.1002/mds.29126.

We performed a systematic review to provide an overview of research involving Parkinson's disease (PD) genetics in underrepresented populations (URP) and set a baseline to measure the future impact of current efforts in those populations. We observed imbalances in PD genetic studies among URPs with Asian participants from Greater China representing the majority of the articles published (57%), and other populations like Blacks were represented in just 4.0% of the publications. This review provides insight into the significant lack of population diversity in PD research highlighting the immediate need for better representation. The Global Parkinson's Genetics Program (GP2) and similar initiatives aim to impact research in URPs, and the early metrics presented here can be used to measure progress in the field of PD genetics in the future.


Genome-wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients

Sarihan IE et al. Pre-Print

The overall identification of copy number variants (CNV) at a genome-wide level has been understudied in PD patients since most studies only screen a few known PD genes. Here we used genome-wide genotyping data from 747 PD patients and 632 ancestry matched controls from LARGE-PD to understand the genome-wide burden of copy number variants in Latinos and its association with disease:

  • Genome-wide copy number burden analysis showed no difference between patients vs. controls
  • Patients were significantly enriched for CNVs overlapping known PD genes (OR: 3.97 [1.69 - 10.5], P = 0.018), with PARK2 showing the strongest burden
  • Patients carrying a CNV in known PD genes present disease symptoms 26 years earlier compared to patients with CNVs in other genes 
  • In Latin America 5.6% of Early-Onset PD patients carry a CNV in PARK2

The distribution and risk effect of GBA variants in a large cohort of PD patients from Colombia and Peru

Velez-Pardo C, Lorenzo-Betancor O, Jimenez-Del-Rio M, Moreno S, Lopera F, Cornejo-Olivas M, Torres L, Inca-Martinez M, Mazzetti P, Cosentino C, Yearout D, Waldherr SM, Zabetian CP, Mata IF. Parkinsonism Relat Disord. 2019 Jun;63:204-208. doi: 10.1016/j.parkreldis.2019.01.030. Epub 2019 Feb 4.

GBA is the most important risk factor for PD, however little is known about its effects in Latinos. Here we screened 602 PD patients and 319 controls from Colombia and Peru. The key findings were:

  • GBA is an important risk factor in this populations too, increase the risk to develop PD around 4.5 and 6.2 fold in Peru and Colombia respectively
  • While frequency in PD patients from Peru is similar to frequency in other countries (5.5%), frequency in Colombia is double (9.9%) due to the presence of a newly described population-specific mutation (p.K198E)
  • Mutations in GBA not only increase the risk to develop PD, but also advances the age at onset by about 8 years.

LARGE-PD: Examining the Genetics of Parkinson’s Disease in Latin America

 Zabetial CP, Mata IF on behalf of the Latin American Research Consortium on the Genetics of PD (LARGE-PD). Mov Disord . 2017 Sep;32(9):1330-1331. doi: 10.1002/mds.27081. Epub 2017 Jun 28.

Mutations located in codons G2019 and R1441 of the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common genetic cause of PD in patients of European origin.Here, we show that, in the LARGE-PD cohort, the combined frequency of these LRRK2 mutations varies substantially across countries in Latin America and is directly  correlated with the estimated proportion of European ancestry at each site. This indicates that the genetic architecture of PD might differ between Latinos and other population groups, as it has been shown in several other diseases, including cancer.

Careers

Careers

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Research News

Research News

...
New Research Collaborative Aims at Closing Minority Health Disparities

With a Cleveland Clinic research co-laboratories award, Drs. Schmit and Mata will establish the Cleveland Clinic Latino Epidemiology (CCLE) Cohort to help close the gap in research participation and health disparities for the Latino population.



...
Characterizing the Genetic Architecture of Parkinson’s Disease in Latinos

To address the lack of diversity in Parkinson’s disease genetic research, Dr. Mata and colleagues conducted the first ever genome-wide association study of Latino Parkinson’s disease patients from South America.



...
Precision Medicine in Migraine Treatment

With their Co-Laboratories Award, Drs. Mata and Ahmed will team up to develop a way to predict patient response to FDA-approved treatments for migraine prevention.



...
NIH Awards $3.1M to Identify Novel Parkinson’s Disease Genes in Latinos

Dr. Mata and collaborators aim to pinpoint therapeutic targets for treatment and improve diagnosis and risk prediction in Latino populations.



...
Understanding Genetics of Parkinson’s Disease in Latinos



...
Multi-National Genetic Study of Parkinson’s Disease in Latinos



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