Dengke Ma, PhD
Associate Professor
Cardiovascular Research Inst
School of Medicine

Most nematodes, including those from the Antarctica and the common model organism C. elegans, can enter "suspended animation" states upon anoxia; they can also be frozen alive and suspend life that can be revived later virtually any long after freezing, unlike many other multicellular organisms. We use both cultured neural stem cells from hibernating Arctic ground squirrels and nematodes with extremophile-like phenotypes recapitulated in the laboratory as discovery tools to understand mechanisms of cellular and physiological resilience. Genes identified from such systems via large-scale experimental screens or computational mining often encode proteins of unusual properties that define novel mechanisms underlying cytoprotection, cellular organelle dynamics and organismic homeostasis in physiology and behaviors. Some were even acquired from extremophile microbes via horizontal gene transfers and functionally co-opted to confer stress resilience. We take advantage of findings from our research and aim to use synthetic physiology approaches to engineer biological systems that may foster new means of cytoprotection, organ transplantation, reversible cryo-preservation and therapeutics to treat ischemic, neurological and age-related disorders.

• Acquired stress resilience through bacteria-to-nematode interdomain horizontal gene transfer.
  The EMBO journal 2023 Pandey T, Kalluraya CA, Wang B, Xu T, Huang X, Guang S, Daugherty MD, Ma DK
• Natural product P57 induces hypothermia through targeting pyridoxal kinase.
  Nature communications 2023 Wang R, Xiao L, Pan J, Bao G, Zhu Y, Zhu D, Wang J, Pei C, Ma Q, Fu X, Wang Z, Zhu M, Wang G, Gong L, Tong Q, Jiang M, Hu J, He M, Wang Y, Li T, Liang C, Li W, Xia C, Li Z, Ma DK, Tan M, Liu JY, Jiang…
• Acquired stress resilience through bacteria-to-nematode horizontal gene transfer.
  bioRxiv : the preprint server for biology 2023 Pandey T, Kalluraya C, Wang B, Xu T, Huang X, Guang S, Daugherty MD, Ma DK
• LPD-3 as a megaprotein brake for aging and insulin-mTOR signaling in C. elegans.
  bioRxiv : the preprint server for biology 2023 Pandey T, Wang B, Wang C, Zu J, Deng H, Shen K, do Vale GD, McDonald JG, Ma DK
• Bridge-Like Lipid Transfer Proteins (BLTPs) in C. elegans: From Genetics to Structures and Functions.
  Contact (Thousand Oaks (Ventura County, Calif.)) 2023 Pandey T, Zhang J, Wang B, Ma DK
• Stress-Induced Phenoptosis: Mechanistic Insights and Evolutionary Implications.
  Biochemistry. Biokhimiia 2022 Pandey T, Ma DK
• GPCR signaling regulates severe stress-induced organismic death in Caenorhabditis elegans.
  Aging cell 2022 Wang C, Long Y, Wang B, Zhang C, Ma DK
• A conserved megaprotein-based molecular bridge critical for lipid trafficking and cold resilience.
  Nature communications 2022 Wang C, Wang B, Pandey T, Long Y, Zhang J, Oh F, Sima J, Guo R, Liu Y, Zhang C, Mukherjee S, Bassik M, Lin W, Deng H, Vale G, McDonald JG, Shen K, Ma DK
• Co-opted genes of algal origin protect C. elegans against cyanogenic toxins.
  Current biology : CB 2022 Wang B, Pandey T, Long Y, Delgado-Rodriguez SE, Daugherty MD, Ma DK
• Abstract TP251: CRISPR-engineered Mouse Neural Cells Expressing An Optimized Manf Variant Reveals Mechanisms Of MANF Neuroprotection.
  Stroke 2022 Ted D Llera, Neel S Singhal, Dengke Ma
• Ethacrynic acid targets GSTM1 to ameliorate obesity by promoting browning of white adipocytes.
  Protein & cell 2021 Cui Z, Liu Y, Wan W, Xu Y, Hu Y, Ding M, Dou X, Wang R, Li H, Meng Y, Li W, Jiang W, Li Z, Li Y, Tan M, Ma DK, Ding Y, Liu JO, Luo C, Yu B, Tang Q, Dang Y
• The C. elegans homolog of human panic-disorder risk gene TMEM132D orchestrates neuronal morphogenesis through the WAVE-regulatory complex.
  Molecular brain 2021 Wang X, Jiang W, Luo S, Yang X, Wang C, Wang B, Dang Y, Shen Y, Ma DK
• The conserved autoimmune-disease risk gene TMEM39A regulates lysosome dynamics.
  Proceedings of the National Academy of Sciences of the United States of America 2021 Luo S, Wang X, Bai M, Jiang W, Zhang Z, Chen Y, Ma DK
• The conserved transmembrane protein TMEM-39 coordinates with COPII to promote collagen secretion and regulate ER stress response.
  PLoS genetics 2021 Zhang Z, Luo S, Barbosa GO, Bai M, Kornberg TB, Ma DK
• Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells.
  eLife 2020 Singhal NS, Bai M, Lee EM, Luo S, Cook KR, Ma DK
• Nucleolus localization of SpyCas9 affects its stability and interferes with host protein translation in mammalian cells.
  Genes & diseases 2020 Tan R, Du W, Liu Y, Cong X, Bai M, Jiang C, Li Z, Tan M, Ma DK, Huang Q, Jiang W, Dang Y
• Resilience to Injury: A New Approach to Neuroprotection?
  Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 2020 Singhal NS, Sun CH, Lee EM, Ma DK
• Broadly conserved roles of TMEM131 family proteins in intracellular collagen assembly and secretory cargo trafficking.
  Science advances 2020 Zhang Z, Bai M, Barbosa GO, Chen A, Wei Y, Luo S, Wang X, Wang B, Tsukui T, Li H, Sheppard D, Kornberg TB, Ma DK
• Neuronal GDPGP1 and glycogen metabolism: friend or foe?
  The Journal of cell biology 2020 Singhal NS, Lee EM, Ma DK
• Abstract TP110: Dissecting the Optimized Cytoprotective Responses of Arctic Ground Squirrels With CRISPR.
  Stroke 2020 Evan M Lee, Neel S Singhal, Meirong Bai, Dengke K Ma
• MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis.
  PLoS biology 2019 Lee D, An SWA, Jung Y, Yamaoka Y, Ryu Y, Goh GYS, Beigi A, Yang JS, Jung GY, Ma DK, Ha CM, Taubert S, Lee Y, Lee SV
• VHL-1 inactivation and mitochondrial antioxidants rescue C. elegans dopaminergic neurodegeneration.
  Protein & cell 2019 Chen S, Luo S, Zhang Z, Ma DK
• Abstract TP136: Mitochondrial Mechanisms of Resilience Revealed by Arctic Ground Squirrel Neural Cells.
  Stroke 2019 Neel S Singhal, Meirong Bai, Shuo Luo, Dengke K Ma
• WDR-23 and SKN-1/Nrf2 Coordinate with the BLI-3 Dual Oxidase in Response to Iodide-Triggered Oxidative Stress.
  G3 (Bethesda, Md.) 2018 Xu Z, Hu Y, Deng Y, Chen Y, Hua H, Huang S, Nie Q, Pan Q, Ma DK, Ma L
• The receptor tyrosine kinase HIR-1 coordinates HIF-independent responses to hypoxia and extracellular matrix injury.
  Science signaling 2018 Vozdek R, Long Y, Ma DK
• A genetic program mediates cold-warming response and promotes stress-induced phenoptosis in C. elegans.
  eLife 2018 Jiang W, Wei Y, Long Y, Owen A, Wang B, Wu X, Luo S, Dang Y, Ma DK
• Conserved roles of C. elegans and human MANFs in sulfatide binding and cytoprotection.
  Nature communications 2018 Bai M, Vozdek R, Hnízda A, Jiang C, Wang B, Kuchar L, Li T, Zhang Y, Wood C, Feng L, Dang Y, Ma DK
• Prolyl 4-hydroxylase 2 promotes B-cell lymphoma progression via hydroxylation of Carabin.
  Blood 2018 Jiang W, Zhou X, Li Z, Liu K, Wang W, Tan R, Cong X, Shan J, Zhan Y, Cui Z, Jiang L, Li Q, Shen S, Bai M, Cheng Y, Li B, Tan M, Ma DK, Liu JO, Dang Y
• Multiple excitatory and inhibitory neural signals converge to fine-tune Caenorhabditis elegans feeding to food availability.
  FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2015 Dallière N, Bhatla N, Luedtke Z, Ma DK, Woolman J, Walker RJ, Holden-Dye L, O'Connor V
• Warm up and cool down!
  Oncotarget 2015 Wang T, Ma D
• Acyl-CoA Dehydrogenase Drives Heat Adaptation by Sequestering Fatty Acids.
  Cell 2015 Ma DK, Li Z, Lu AY, Sun F, Chen S, Rothe M, Menzel R, Sun F, Horvitz HR
• CYP-13A12 of the nematode Caenorhabditis elegans is a PUFA-epoxygenase involved in behavioural response to reoxygenation.
  The Biochemical journal 2014 Keller J, Ellieva A, Ma DK, Ju J, Nehk E, Konkel A, Falck JR, Schunck WH, Menzel R
• Cytochrome P450 drives a HIF-regulated behavioral response to reoxygenation by C. elegans.
  Science (New York, N.Y.) 2013 Ma DK, Rothe M, Zheng S, Bhatla N, Pender CL, Menzel R, Horvitz HR
• The neurobiology of sensing respiratory gases for the control of animal behavior.
  Frontiers in biology 2012 Ma DK, Ringstad N
• CYSL-1 interacts with the O2-sensing hydroxylase EGL-9 to promote H2S-modulated hypoxia-induced behavioral plasticity in C. elegans.
  Neuron 2012 Ma DK, Vozdek R, Bhatla N, Horvitz HR
• Neuronal activity modifies the DNA methylation landscape in the adult brain.
  Nature neuroscience 2011 Guo JU, Ma DK, Mo H, Ball MP, Jang MH, Bonaguidi MA, Balazer JA, Eaves HL, Xie B, Ford E, Zhang K, Ming GL, Gao Y, Song H
• Bridging Environment and DNA: Activity-Induced Epigenetic Modification in the Adult Brain.
  Two Faces of Evil: Cancer and Neurodegeneration 2011 Dengke K. Ma, Junjie U. Guo, Guo-li Ming, Hongjun Song
• Epigenetic choreographers of neurogenesis in the adult mammalian brain.
  Nature neuroscience 2010 Ma DK, Marchetto MC, Guo JU, Ming GL, Gage FH, Song H
• Oxysterols drive dopaminergic neurogenesis from stem cells.
  Cell stem cell 2009 Ma DK, Ming GL, Song H
• Activity-dependent extrinsic regulation of adult olfactory bulb and hippocampal neurogenesis.
  Annals of the New York Academy of Sciences 2009 Ma DK, Kim WR, Ming GL, Song H
• Molecular genetic analysis of FGFR1 signalling reveals distinct roles of MAPK and PLCgamma1 activation for self-renewal of adult neural stem cells.
  Molecular brain 2009 Ma DK, Ponnusamy K, Song MR, Ming GL, Song H
• Adult neural stem cells in the mammalian central nervous system.
  Cell research 2009 Ma DK, Bonaguidi MA, Ming GL, Song H
• DNA excision repair proteins and Gadd45 as molecular players for active DNA demethylation.
  Cell cycle (Georgetown, Tex.) 2009 Ma DK, Guo JU, Ming GL, Song H
• Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis.
  Science (New York, N.Y.) 2009 Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, Flavell RA, Lu B, Ming GL, Song H
• G9a and Jhdm2a regulate embryonic stem cell fusion-induced reprogramming of adult neural stem cells.
  Stem cells (Dayton, Ohio) 2008 Ma DK, Chiang CH, Ponnusamy K, Ming GL, Song H
• Cellular niches for endogenous neural stem cells in the adult brain.
  CNS & neurological disorders drug targets 2007 Jordan JD, Ma DK, Ming GL, Song H
• Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain.
  Cell 2007 Duan X, Chang JH, Ge S, Faulkner RL, Kim JY, Kitabatake Y, Liu XB, Yang CH, Jordan JD, Ma DK, Liu CY, Ganesan S, Cheng HJ, Ming GL, Lu B, Song H
• Glial influences on neural stem cell development: cellular niches for adult neurogenesis.
  Current opinion in neurobiology 2005 Ma DK, Ming GL, Song H
• Adult neural stem cells and repair of the adult central nervous system.
  Journal of hematotherapy & stem cell research 2003 Goh EL, Ma D, Ming GL, Song H