Catarina Maria Quinzii, MD

  • Associate Professor of Neurology at CUMC
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Overview

Dr. Quinzii’s laboratory focuses on mitochondrial diseases. One of our main interests is Coenzyme Q10 (CoQ10) deficiency. CoQ deficiency comprises clinically and genetically heterogeneous diseases that are variably responsive to CoQ10 supplementation. This heterogeneity in clinical presentation and in therapeutic response indicates that multiple pathomechanisms exist, which is consistent with the multiple function of CoQ10, a mitochondrial lipid which functions mainly as an electron carrier in the mitochondrial respiratory chain and as antioxidant in cell membranes. We have identified molecular defects underlying primary and secondary CoQ10 deficiency, and we have been studying the pathomechanisms of CoQ10 deficiencies in mammalian cells and animal models.

The most common phenotypes associated with CoQ10 deficiency is cerebellar ataxia. Although cerebellum seems to be selectively vulnerable to low levels of CoQ, the mechanisms underlying CoQ10 deficiency in cerebellar ataxia, and the role of CoQ10 deficiency in the pathogenesis or progression of the disease are undefined. We and other groups reported CoQ10 deficiency in muscle and/or fibroblasts of patients carrying mutations in APTX, encoding aprataxin (APTX), cause of the autosomal recessive ataxia-oculomotor-apraxia 1 (AOA1). In order to understand the link between cerebellar ataxia and CoQ10 deficiency, we studied APTX mutant and depleted cells, and we found that lack of aprataxin causes reduction of the pathway APE1/NRF1/NRF2, and their target genes. One of the goals of our research is to characterize the pathogenic significance of this novel nuclear-mitochondrial crosstalk pathway in cerebellar ataxia. Understanding mechanisms underlying mitochondrial dysfunction in cerebellar ataxia is important for the development of novel therapeutic approaches for this and other neurodegenerative diseases with secondary mitochondrial involvement.

The second most common phenotype is nephrotic syndrome. Although patients with this manifestation often respond to CoQ10 supplementation, the mechanism of action of CoQ10 is not clear. CoQ10 is an electron acceptor for sulfide quinone reductase (SQR), the first enzyme of the oxidation pathway of hydrogen sulfide (H2S), a mitochondrial substrate and gas modulator involved in several physiological functions. Our recent in vitro and in vivo studies have demonstrated that CoQ10 deficiency causes impairment of H2S oxidation, proportional to the residual levels of CoQ10. We are investigating the role of sulfides oxidation impairment in CoQ10 deficiency and the role of CoQ10 as physiological regulator of this pathway.

Patients with CoQ10 deficiency partially respond to supplementation; the efficacy of CoQ10 supplementation is hampered by the poor bioavailability of this compound particularly in the brain. Our group has been working on understanding mechanisms of action of CoQ10 and its analogs and in testing suitable alternative or complementary therapy, as the up-regulation of endogenous CoQ10 biosynthesis.

More recently, we have identified an autosomal recessive the gene encoding the required for meiotic nuclear division 1 (RMND1) protein causing an infantile multisystemic disease and defective mitochondrial protein synthesis. RMND1 protein belongs to an evolutionary conserved family of unknown function proteins sharing the DUF155 domain. Mutations in DUF155 containing proteins have never been associated with a human disease. Therefore, we have developed in vitro and in vivo systems to understand the function of RMND1.

Academic Appointments

  • Associate Professor of Neurology at CUMC

Languages

  • Italian

Gender

  • Female

Credentials & Experience

Education & Training

  • MD, 1999 Universita Statale di Milano (Italy)
  • Fellowship: 2006 Columbia University Medical Center

Honors & Awards

  • 2022: R21 Exploratory/Developmental Research Award (NIH)
  • 2020: Focused program award (DoD)
  • 2018: Research Seed money grant (NAF)
  • 2015: Research partnership award (DoD)
  • 2014: PO1 Research Program project grant (NIH)
  • 2014: Research grant (MDA)
  • 2010: K23 Mentored Patient-Oriented Career development award (NIH)


Research