Xi Huang Lab
Ion channels in brain development and tumourigenesis
Ion channels are pore-forming transmembrane proteins that regulate biological processes by controlling ion flow across cell membranes. At a cross disciplinary field, the roles of ion channels in cancer remain under-explored. Using multi-disciplinary approaches such as Drosophila genetics, mouse genetics, xenograft modeling, cell biology, and electrophysiology, our lab studies the mechanisms by which ion channels regulate brain development and tumourigenesis, and the therapeutic efficacy of ion channel drugs in treating brain tumours.
We are asking the following questions in the lab:
- At the systematic level, what is the mutational landscape of ion channels in various cancer types, and how do recurrent ion channel mutations affect tumourigenesis?
- At the cellular level, how do ion channels regulate tumour initiation, progression and metastasis in genetically tractable animal models?
- At the molecular level, how do different ion channels form a functional network to regulate cancer cell behaviors?
- Can we use ion channel-targeting drugs for cancer treatment?
Scientist – Developmental & Stem Cell Biology Program
Principal Investigator – Arthur & Sonia Labatt Brain Tumour Research Centre
Assistant Professor – Department of Molecular Genetics, University of Toronto
Ion channel function in brain cancer
- Huang X*, He Y*, Dubuc AM*, Hashizume R, Zhang W, Reimand J, Yang H, Wang TA, Stehbens S, Younger S, Barshow S, Zhu S, Cooper MK, Peacock J, Ramaswamy V, Garzia L, Wu X, Remke M, Forester CM, Kim CC, Weiss WA, James CD, Shuman MA, Bader GD, Mueller S, Taylor MD, Jan YN, Jan LY. (2015) EAG2 potassium channel with evolutionarily conserved function as a brain tumor target. Nat. Neurosci. 18(9): 1236-46. (* contributed equally) PMID: 26258683
Channeling brain cancer. Sci. Signal. (2015): 8 (392), ec245
Therapy: Reinventing the wheel. Nature Reviews Cancer (2015): 15, 514
EAG2 potassium channel: A new regulator of malignancy and therapeutic target in medulloblastoma Neuro-Oncology (2015) 17(12), 1547
Voltage spikes driving medulloblastoma. Cancer Res (2015): 75, 4439
Common class of “channel blocking” drugs may find a role in cancer therapy ScienceDaily, EurekaAlert!, Neuroscientist News, Newswise, HealthCanal, UCSF News Center
Potassium Channel Blockers Show Promise as Treatment for Brain Tumors OncoTherapy Network
Targeting an Ion Channel to Treat Common Pediatric Brain Tumor Northwestern University News Center
- Huang X# and Jan LY#. (2014) Targeting potassium channels in cancer. J Cell Biol. 206(2): 151-62. (# co-corresponding authors) PMID: 25049269
- Huang X, Dubuc AM, Hashizume R, Berg J, He Y, Wang J, Chiang C, Cooper MK, Northcott PA, Taylor MD, Barnes MJ, Tihan T, Chen J, Hackett CS, Weiss WA, James CD, Rowitch DH, Shuman MA, Jan YN, Jan LY. (2012) Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics. Genes Dev. 15; 26(16): 1780-96. (Cover Article) PMID: 22855790
Medulloblastoma: Pump up the volume. Nature Reviews Cancer, 12, 583
Targeting ion channels. Nature Structural & Molecular Biology, 19, 867
Ion Channel Activity Promotes Mitotic Entry and Tumor Cell Growth. Cancer Discovery, 2, 763
Sonic hedgehog signaling in development and disease
- Huang X, Liu J, Ketova T, Fleming JT, Grover VK, Cooper MK, Litingtung Y, Chiang C. (2010) Transventricular delivery of Sonic hedgehog is essential to cerebellar ventricular zone development. Proc Natl Acad Sci U S A. 107(18): 8422-7. PMID: 20400693
- Huang X, Sarangi A, Ketova T, Litingtung Y, Cooper MK, Chiang C. (2010) Intracranial orthotopic allografting of medulloblastoma cells in immunocompromised mice. J Vis Exp. (44). pii: 2153. PMID: 20972404
- Cheng FY*, Huang X*, Sarangi A, Ketova T, Cooper MK, Litingtung Y, Chiang C. (2012) Widespread contribution of Gdf7 lineage to cerebellar cell types and implications for Hedgehog-driven medulloblastoma formation PLoS ONE, 7(4): e35541. (* contributed equally) PMID: 22539980
- Huang X, Ketova T, Litingtung Y, Chiang C. (2010) Isolation, enrichment and maintenance of medulloblastoma stem cells. J Vis Exp. (43). pii: 2086. PMID: 20834221
- Huang X, Ketova T, Fleming JT, Wang H, Dey SK, Litingtung Y, Chiang C. (2009) Sonic hedgehog signaling regulates a novel epithelial progenitor domain of the hindbrain choroid plexus. Development. 136(15): 2535-43. PMID: 19570847
Shh, choroid plexus growth in progress. Development (2009) 136: e1502
- Huang X, Litingtung Y, Chiang C. (2007) Region-specific requirement for cholesterol modification of sonic hedgehog in patterning the telencephalon and spinal cord. Development. 134(11): 2095-10 PMID: 17507410
- Oh S*, Huang X*, Liu J, Litingtung Y, Chiang C. (2009) Shh and Gli3 activities are required for timely generation of motor neuron progenitors. Developmental Biology. 331(2): 261-9. (* contributed equally) PMID: 19433083
- Huang X*, Goudy SL*, Ketova T, Litingtung Y, Chiang C. (2008) Gli3-deficient mice exhibit cleft palate associated with abnormal tongue development. Dev Dyn. 237(10): 3079-87 (* contributed equally) PMID: 18816854
- Huang X, Litingtung Y, Chiang C. (2007) Ectopic sonic hedgehog signaling impairs telencephalic dorsal midline development: implication for human holoprosencephaly. Hum Mol Genet. 16(12): 1454-68. PMID: 17468181
- Agnihotri S, Golbourn B, Huang X, Remke M, Younger S, Cairns RA, Chalil A, Smith CA, Krumholtz SL, MacKenzie D, Rakopoulos P, Ramaswamy V, Taccone MS, Mischel PS, Fuller GN, Hawkins C, Stanford WL, Taylor MD, Zadeh G, Rutka JT. (2016) PINK1 is a Negative Regulator of Growth and the Warburg Effect in Glioblastoma. Cancer Res. 2016 June 20. PMID: 2732564
- Morrissy AS*, Garzia L*, Shih DJH, Zuyderduyn S, Huang X, Skowron P, Remke M, Cavalli FMG, Ramaswamy V, Lindsay P, Jelveh S, Donovan LK, Wang X, Luu B, Zayne K, Li Y, Mayoh C, Thiessen N, Mercier E, Mungall KL, Yusanne M, Tse K, Zeng T, Shumansky K, Roth AJL, Shah S, Farooq H, Kijima N, Holgado BL, Lee JJY, Matan-Lithwick S, Liu J, Mack SC, Manno A, Michaelraj KA, Nor C, Peacock J, Qin L, Reimand J, Rolider A, Thompson YY, Wu X, Pugh T, Ally A, Bilenky M, Butterfied YSN, Carlsen R, Cheng Y, Chuah E, Corbett RD, Dhalla N, He A, Lee D, Li HI, Long W, Mayo M, Plettner P, Qian JQ, Schein JE, Tam A, Wong T, Birol I, Zhao Y, Faria CC, Pimentel J, Bendel AE, Fults DW, Walter AW, Kumabe T, Tominaga T, Collins VP, Cho YJ, Hoffman C, Lyden D, Wisoff J, Garvin JH, Stearns DS, Massimi L, Schuller U, Sterba J, Zitterbart K, Puget S, Ayrault O, Dunn SE, Tirapelli DPC, Carlotti CG, Wheeler H, Hallahan AR, Ingram W, MacDonald TJ, Olson JJ, Van Meir EG, Lee JY, Wang KC, Kim SK, Cho BK, Pietsch T, Fleischack G, Tippelt S, Ra YS, Bailey S, Lindsay JC, Clifford SC, Eberhart CG, Cooper MK, Packer R, Massimino M, Garre ML, Bartels U, Tabori U, Hawkins C, Dirks P, Bouffet E, Rutka JT, Wechsler-Reya RJ, Weiss WA, Collier LS, Dupuy AJ, Korshunov A, Jones DTW, Kool M, Northcott PA, Pfister SM, Largaespada DA, Mungall AJ, Moore RA, Jabado N, Bader GD, Jones JM, Malkin D, Marra MA#. Taylor MD#. (2015) Divergent Clonal Selection Drives Medulloblastoma at Recurrence. Nature, 529, 351–357 (* contributed equally, # co-corresponding authors). PMID: 26760213
- Song Y, Sretavan D, Salegio E, Berg J, Huang X, Cheng T, Xiong X, Meltzer S, Han C, Nguyen TT, Bresnahan JC, Beattie MS, Jan LY, Jan YN. (2015) Regulation of axon regeneration by the RNA repair and splicing pathway. Nat. Neurosci. 18(6): 817-25. PMID: 25961792
- Hashizume R, Andor N, Ihara Y, Lerner R, Gan H, Chen X, Fang D, Huang X, Tom MW, Ngo V, Solomon D, Mueller S, Paris PL, Zhang Z, Petritsch C, Gupta N, Waldman TA, James CD. (2014) Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat Med. (12): 1394-1396. PMID: 25401693
- Fogel JL, Chiang C, Huang X, Agarwala S. (2008) Ventral specification and perturbed boundary formation in the mouse midbrain in the absence of Hedgehog signaling. Dev Dyn. 237(5): 1359-72. PMID: 18429041
- Oh S, Huang X, Chiang C. (2005) Specific requirements of sonic hedgehog signaling during oligodendrocyte development. Dev Dyn. 234(3): 489-96. PMID: 15880651
Be part of our team
We always wish to hear from talented candidates who are interested in joining our lab.
There are two priorities in the Huang lab:
1. Performing mechanistic studies to discover the unknown functions of ion channels during development and tumourigenesis
2. Realizing the best potential and fostering the career development of all lab members
Before every lab member joins, both scientific and career goals will be discussed with the PI, and a plan to achieve these goals will be laid out. Both postdoctoral fellows and graduate students will be able to choose from a number of projects depending on his/her interests, and they are encouraged to test their own ideas and develop new directions.
Postdoctoral fellows are expected to independently lead projects with input from the PI and other lab members. While graduate students will initially work closely with the PI and senior members in the lab, they will also be fostered to develop independence and become the pilots of their projects.
Besides the general lab duties, lab manager and research assistants are also encouraged to take on scientific projects depending on his/her interests and talents. Everyone is expected to work smart and do the best science, and the PI will make every effort to develop a collegial lab environment and promote the professional growth of all lab members.
The lab succeeds when its members succeed!
Prospective postdoctoral fellows can apply directly by sending their CV and cover letter outlining their research interests to Dr. Huang
Undergraduate students can join the lab as long as they are enrolled in any department at a recognized university
Dr. Xi Huang
Peter Gilgan Centre for Research and Learning
686 Bay Street, Room 16.9704
Toronto, ON M5G 0A4
Office: (416) 813-7654 Ext: 309526
Main Lab: 16.9420 (Ext: 309527)
Fly Lab: 15.9400 (Ext: 309528)