Andrew Munkacsi

Dr Andrew Munkacsi profile picture

Chemical Genetics School of Biological Sciences

Courses

Teaching in 2020

Personal Bio

PhD University of Minnesota I MSc University of Illinois I BSc Southern Illinois University

Trained at Columbia University Medical Center and the University of Minnesota, I am a translational research scientist using high-throughput genomic, lipidomic, and metabolomic approaches to investigate human disease, human nutrition, molecular evolution, and functional biodiversity. I am a teacher and mentor that establishes classrooms and laboratories as interactive, intellectually fearless environments that inspire an enduring appreciation for the interconnectedness of disciplines within biology from the molecular to the organismal level. My laboratory at Victoria University of Wellington opens July 2012.

Research interests

My research interests are at the interface of genomics, medicine, and biodiversity. The overall objective within my laboratory is to identify novel targets to treat the defective transport of lipids and glucose in human diseases. To identify these targets, we use a unique combination of unbiased, high-throughput systems biology approaches in yeast genomic screens and exome sequencing of human patients. These results are then translated and validated with experiments in animal models and human patient cells. In addition to identifying novel therapeutic targets to treat human diseases, our results also help understand the basic biology of lipid and glucose homeostasis in all eukaryotic cells. Specific projects for which I am recruiting students include but are not limited to the following:

  • Translational genomics to treat defective cholesterol and sphingolipid transport in human neurodegenerative diseases. To identify modifiers of neurodegeneration associated with the defective intracellular transport of cholesterol and sphingolipids, we use a suite of unbiased, high-throughput chemical genomic screens in yeast based on synthetic lethality, gene expression, protein localization, and protein-protein interactions. We have successfully used these genome-wide yeast screens to identify unsuspected and precise targets to treat neurodegenerative diseases such as Alzheimer’s disease and Niemann-Pick Type C disease (Munkacsi et al. 2011), and my lab continues to use genome-wide screens to further investigate these and additional neurodegenerative diseases.
  • HDAC inhibitors as a candidate therapy to treat a fatal pediatric disease. There is currently no effective therapy to treat Niemann-Pick Type C (NPC) disease, a fatal pediatric neurodegenerative disease caused by an intracellular accumulation of cholesterol and sphingolipids. In cells derived from patients with NPC disease, we identified that histone deacetylase (HDAC) inhibitors ameliorate the lipid accumulation that causes NPC disease (Munkacsi et al. 2011). We are now testing the efficacy of HDAC inhibitors to ameliorate lipid accumulation and neurodegeneration in animal models of NPC disease and defining the molecular mechanisms of this candidate treatment. Cholesterol transport as a mechanism for treatment of Alzheimer’s disease with HDAC inhibitors.
  • Cholesterol is a major risk factor for Alzheimer’s disease (AD). In encouraging recent studies, cognitive defects in mouse models of AD have been successfully rescued by HDAC inhibition, yet the mechanisms underlying this promising treatment have not been fully described. To determine if the rescue of memory deficits by HDAC inhibition is accomplished through an improvement in cholesterol metabolism, we are characterizing cholesterol homeostasis and biomarkers of AD in cell and animal models of AD treated with HDAC inhibitors.
  • Functional biodiversity and -omics of wild fungi in New Zealand. The unique and extreme environments of New Zealand are unexplored sources of functional biodiversity. Students participating in this project will have the opportunity to tramp and work outside in the New Zealand bush; they will collect fungi (mushrooms and yeasts) from specific niches and identify these fungi using the Phylogenetic Species Concept (Munkacsi et al. 2007). Then we will use genomic, lipidomic, and metabolomic strategies to define the molecular natural history of these species and these unique niches. Ecology and Biodiversity students are invited to participate in this project.
  • Next-generation exome sequencing to identify disease modifier loci. The modifiers of human diseases that we identify using yeast genomics cannot represent all genetic modifiers since humans have ~4 times more genes than yeast. To identify modifiers that are not dependent on evolutionary conservation, we are currently sequencing and analyzing the exomes (all exons in the human genome) of human patients. Computer Science and Biotechnology students are invited to participate in this project.
  • Nutritional genomics of homeopathic dietary supplements. Natural dietary supplements are consumed daily in New Zealand and throughout the world. Since these products are not regulated by government agencies, the biology behind their positive effects on human health is often not known. We use functional genomics to identify the genetic targets of these supplements and elucidate the pathways through which these supplements are metabolised.

Publications

Munkacsi AB, Chen FW, Brinkman MA, Higaki K, Dominguez G, Chaudhari J, Layer JV, Tong A, Bard M, Boone C, Ioannou YA, Sturley SL (2011) An ‘exacerbate-reverse’ strategy in yeast identifies histone deacetylase inhibition as a correction for cholesterol and sphingolipid transport defects in human Niemann-Pick type C disease. Journal of Biological Chemistry, 286, 23842-23851.

  • Paper of the Week in Journal of Biological Chemistry (1 of 100 papers out of the ~7,000 papers published each year in the Journal of Biological Chemistry)

Shechtman CF, Henneberry AL, Seimon TA, Tinkelenberg AH, Wilcox LJ, Lee E, Fazlollahi M, Munkacsi AB, Bussemaker HJ, Tabas IA, Sturley SL (2011) Loss of subcellular lipid transport due to ARV1 deficiency disrupts organelle homeostasis and activates the unfolded protein response. Journal of Biological Chemistry, 286, 11951-11959.

Gulati S, Liu Y, Munkacsi AB, Wilcox L, Sturley SL (2010) Sterols and sphingolipids: Dynamic duo or partners in crime? Progress in Lipid Research, 49, 353-365.

Munkacsi AB, Pentchev PG, Sturley SL (2009) Spreading the wealth: Niemann-Pick type C proteins bind and transport cholesterol. Cell Metabolism, 10, 3-4.

Dentinger BT, Lodge DJ, Munkacsi AB, Desjardin DE, McLaughlin DJ (2009) Phylogenetic placement of an unusual coral mushroom challenges the classic hypothesis of strict coevolution in the Apterostigma pilosum group ant-fungus mutualism. Evolution, 63, 2172-2178.

View more publications at ResearchGate

Courses

Teaching in 2020