Xi Huang Lab

 

calligraphy by Daming Huang

We do curiosity-driven and serendipitous science to
decode mechano-electrical-chemical signaling in cancer

POTASSIUM CHANNEL IN A DIVIDING CELL BRAIN TUMOUR AND METASTASIS ELECTRICAL ACTIVITY IN A TUMOUR CELL NEURAL PROGENITOR CELLS IN CEREBELLUM PURKINJE NEURONS FLY BRAIN TUMOUR FLY BRAIN TUMOUR CELLS

Research

We study physical properties and mechano-electrical-chemical signaling in cancer. While extensive research has informed genetics and biochemical mechanisms in tumorigenesis, how mechanical and electrical signaling regulate cancer is less defined. Ion channels govern cell behaviors by perceiving physicochemical cues (mechanical force, membrane voltage, temperature, pH etc.) to control ion flux across membranes. We ask the following questions:

 

  • At the systematic level, what are the mutational landscape and functional alterations of ion channels in cancer?
  • At the tissue level, how do ion channels regulate tumor initiation, progression, metastasis, and drug resistance in genetically tractable animal models? 
  • At the cellular level, how do ion channels perceive physicochemical cues to control cancer cell state?
  • 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 to treat cancer?

 

Using multi-disciplinary approaches in bioinformatics, Drosophila and mouse genetics, xenograft modeling, advanced imaging, electrophysiology, and bioengineering, we discover disease mechanisms and therapeutic vulnerabilities at the interface of cancer biology, neuroscience, and mechanobiology.

Funding partners

Sickkids Foundation
Garron Family Cancer Centre
Click here to visit the Brain Tumour Research Centre website
Click here to visit the Canadian Institutes of Health Research website
Click here to visit the NSERC website
Click here to visit the Canadian Cancer Society website
Click here to visit the American Brain Tumour Association website
Click here to visit the Cancer Research Society website
Click here to visit the Concern Foundation website
Click here to visit the Meagan's walk website
Click here to visit the Brainchild website
Click here to visit the RDMM network website
Click here to visit the University of Toronto website
Click here to visit the Ontario Institute of Cancer Research website
Click here to visit the US Department of Defence website
Click here to visit the Canada Research Chair website
Click here to visit the Sontag Foundation website

People

Xi Huang, PhD

Canada Research Chair – Cancer Biophysics

Scientist – Developmental & Stem Cell Biology Program

Scientist – Arthur & Sonia Labatt Brain Tumour Research Centre

Assistant Professor – Department of Molecular Genetics, University of Toronto

Kamilia Talipova

Research Technologist I

Education:

B.Sc. Department of Biology, York University

Xin ChenXin Chen, PhD

Postdoctoral Fellow

Education:

PhD – Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences

Namal Abeysundara, PhD

Postdoctoral Fellow
Co-supervised by Dr. Michael Taylor

Education:

PhD – Medical Sciences, Department of Medical Genetics, University of Alberta

Shahrzad Bahrampour - Research FellowShahrzad Bahrampour, PhD

Postdoctoral Fellow

 

Education:

PhD – Medical Science, Linköping University

Jerry FanJerry Fan, B.Sc.

Graduate Student
Department of Molecular Genetics

Education:

B.Sc. – Department of Pharmacology, McGill University

Weifan DongWeifan Dong, B.Sc.

Graduate Student
Department of Molecular Genetics

Education:

B.Sc. –  Institute of Life Sciences, Zhejiang University

Ali Momin, B.Sc.

Graduate Student
Department of Molecular Genetics

Education:

B.Sc. –  Specialization in Biology, Department of Cell & Systems Biology, University of Toronto

Nicolaes Min B.Sc.

Graduate Student
Department of Molecular Genetics

Education:

B.Sc. – Specialization in Biochemistry, Department of Chemistry, University of Toronto

Jade Chan B.Sc.

Graduate Student
Department of Molecular Genetics
Co-supervised by Dr. C.C. Hui

Education:

B.Sc. – Co-operative Program, Major: Honours Psychology, Minor: Biology, University of Waterloo

Xian Wang, Postdoctoral FellowXian Wang, PhD

Postdoctoral Fellow

Education:

PhD – Mechanical Engineering, University of Toronto

Publications

BY TOPICS (SELECTED PUBLICATIONS)
Mechanosensitive ion channel in brain cancer
  • Chen X, Wanggou S, Bodalia A, Zhu M, Dong W, Fan JJ, Yin WC, Min HK, Hu M, Draghici D, Dou W, Li F, Coutinho FJ, Whetstone H, Kushida MM, Dirks PB, Song Y, Hui CC, Sun Y, Wang LY, Li X, and Huang X (2018) A feedforward mechanism mediated by mechanosensitive ion channel PIEZO1 and tissue mechanics promotes glioma aggression. Neuron 100(4):799-815.e7. PMID:30344046

        Editorial highlights:

        Video abstract: How brain tumors stiffen and grow

        Preview: Unlocking the dangers of a stiffening brain

        F1000Prime Recommended

        Best of Neuron 2018-2019

Media coverage:

May the force not be with you SickKids NewsCancer Stem Cell News

Researchers find a new way to address the challenge of brain tumour “stiffness” OICR News

调节肿瘤组织机械特性或可成为肿瘤治疗新方式 BioArt

 

Potassium channel 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. Nature Neuroscience 18(9): 1236-46. (* contributed equally, # co-corresponding authors) PMID: 26258683

Editorial highlights:

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

Targeting ion channels in cancer. Lab Animal (2015): 44, 370

Media coverage:

Common class of “channel blocking” drugs may find a role in cancer therapy ScienceDailyEurekaAlert!Technology NetworksNewswiseHealthCanal, UCSF News

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

Ion Channels May Play a Role in a New Generation of Cancer Therapies Icagen

 

  • 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 & Development 15; 26(16): 1780-96. (Cover Article) PMID: 22855790

Editorial highlights:

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

 

Chloride channel in brain cancer
  • Francisco MA, Wanggou S, Fan JJ, Dong W, Chen X, Momin A, Abeysundara N, Min HK, Chan J, McAdam R, Sia M, Pusong RJ, Liu S, Patel N, Ramaswamy V, Kijima N, Wang LY, Song Y, Kafri R, Taylor MD, Li X#, Huang X# (2020) Chloride intracellular channel 1 cooperates with potassium channel EAG2 to promote medulloblastoma growth. Journal of Experimental Medicine 217.5: e20190971 (# co-corresponding authors) PMID:32097463

Media coverage:

Study shows common cell protein could be targeted to treat childhood brain cancers OICR News

氯离子通道CLIC1在髓母细胞瘤的致病作用机制 BioArt

 

Sodium channel in brain cancer
  • Pigott BJ, Peters CJ, He Y, Huang X, Younger S, Jan LY, Jan YN (2019) Paralytic, the Drosophila voltage-gated sodium channel, regulates proliferation of neural progenitors. Genes & Development 1;33(23-24):1739-1750. PMID:31753914

 

Review on ion channels in cancer
  • Momin A*,#, Bahrampour S*, Min HK*, Chen X*, Wang X, Sun Y, Huang X# (2021) Channeling force in the brain: mechanosensitive ion channels choreograph mechanics and malignancies. Trends in Pharmacological Sciences (Cover Article) doi.org/10.1016/j.tips.2021.02.006

 

  • Fan JJ# and Huang X# (2020) Ion channels in cancer: orchestrators of electrical signaling and cellular crosstalk. Reviews of Physiology, Biochemistry and Pharmacology (# co-corresponding authors) PMID: 32894333

 

  • Huang X# and Jan LY# (2014) Targeting potassium channels in cancer. Journal of Cell Biology 206(2): 151-62. (# co-corresponding authors) PMID: 25049269
BY YEARS (ALL PUBLICATIONS)
2015 – Present (The Hospital for Sick Children, University of Toronto)
  • Momin A*,#, Bahrampour S*, Min HK*, Chen X*, Wang X, Sun Y, Huang X# (2021) Channeling force in the brain: mechanosensitive ion channels choreograph mechanics and malignancies. Trends in Pharmacological Sciences (Cover Article) doi.org/10.1016/j.tips.2021.02.006

 

  • Shahzad U, Taccone M, Kumar S, Okura H, Krumholtz S, Ishida J, Mine C, Gouveia K, Edgar J, Smith C, Hayes M, Huang X, Derry BW, Taylor MD, and Rutka JT. Modeling human brain tumours in flies, worms, and zebrafish: From proof of principle to novel therapeutic targets. Neuro-Oncology. doi: 10.1093/neuonc/noaa306. PMID: 33378446

 

  • Fan JJ# and Huang X# (2020) Ion channels in cancer: orchestrators of electrical signaling and cellular crosstalk. Reviews of Physiology, Biochemistry and Pharmacology (# co-corresponding authors) PMID: 32894333

 

  • Francisco MA, Wanggou S, Fan JJ, Dong W, Chen X, Momin A, Abeysundara N, Min HK, Chan J, McAdam R, Sia M, Pusong RJ, Liu S, Patel N, Ramaswamy V, Kijima N, Wang LY, Song Y, Kafri R, Taylor MD, Li X#, Huang X# (2020) Chloride intracellular channel 1 cooperates with potassium channel to promote medulloblastoma growth. Journal of Experimental Medicine 217.5: e20190971 (# co-corresponding authors) PMID:32097463

 

  • Pigott BJ, Peters CJ, He Y, Huang X, Younger S, Jan LY, Jan YN (2019) Paralytic, the Drosophila voltage-gated sodium channel, regulates proliferation of neural progenitors. Genes & Development 1;33(23-24):1739-1750. PMID:31753914

 

  • Suzuki H*, Kumar SA*, Shuai S, Diaz-Navarro A, Gutierrez-Fernandez A, De Antonellis P, Cavalli FMG, Juraschka K, Farooq H, Shibahara I, Vladoiu MC, Zhang J, Abeysundara N, Przelicki D, Skowron P, Gauer N, Luu B, Daniels C, Wu X, Forget A, Momin A, Wang J, Dong W, Kim SK, Grajkowska WA, Jouvet A, Fèvre-Montange M, Garrè ML, Nageswara Rao AA, Giannini C, Kros JM, French PJ, Jabado N, Ng HK, Poon WS, Eberhart CG, Pollack IF, Olson JM, Weiss WA, Kumabe T, López-Aguilar E, Lach B, Massimino M, Van Meir EG, Rubin JB, Vibhakar R, Chambless LB, Kijima N, Klekner A, Bognár L, Chan JA, Faria CC, Ragoussis J, Pfister SM, Goldenberg A, Wechsler-Reya RJ, Bailey SD, Garzia L, Morrissy AS, Marra MA, Huang X, Malkin D, Ayrault O, Ramaswamy V, Puente XS, Calarco JA, Stein L, Taylor MD (2019) Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma. Nature 574(7780):707-711. PMID:31664194 (* contributed equally)

 

  • Wang YA, Li XL, Mo YZ, Fan CM, Tang L, Xiong F, Guo C, Xiang B, Zhou M, Ma J, Huang X, Wu X, Li Y, Li GY, Zeng ZY, Xiong W (2018) Effects of tumor metabolic microenvironment on regulatory T cells. Molecular Cancer 17(1):168. PMID:30477520

 

  • Chen X, Wanggou S, Bodalia A, Zhu M, Dong W, Fan JJ, Yin WC, Min HK, Hu M, Draghici D, Dou W, Li F, Coutinho FJ, Whetstone H, Kushida MM, Dirks PB, Song Y, Hui CC, Sun Y, Wang LY, Li X, and Huang X (2018) A feedforward mechanism mediated by mechanosensitive ion channel PIEZO1 and tissue mechanics promotes glioma aggression. Neuron 100(4):799-815.e7. PMID:30344046

 

  • Frattini V, Pagnotta SM, Tala, Fan JJ, Russo MV, Lee SB, Garofano L, Zhang J, Shi P, Lewis G, Sanson H, Frederick V, Cerulo L, Rolland DCM, Mall R, Mokhtari K, Elenitoba-Johnson KSJ, Sanson M, Huang X, Ceccarelli M, Lasorella A, Iavarone A (2018) A metabolic function of FGFR3-TACC3 gene fusions in cancer. Nature 553, 222–227. PMID:29323298

 

  • Park NI, Guilhamon P, Desai K, McAdam RF, Langille E, O’Connor M, Lan X, Whetstone H, Coutinho FC, Vanner RJ, Ling E, Prinos P, Lee L, Selvadurai, H, Atwal G, Kushida M, Clarke ID, Voisin V, Cusimano MD, Bernstein M, Das S, Bader G, Arrowsmith CH, Angers S, Huang X, Lupien M, Dirks PB. (2017) ASCL1 reorganizes chromatin to direct neuronal fate and suppress tumorigenicity. Cell Stem Cell 21(2):209-224.e7. PMID: 28712938

 

  • 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 Research 76(16):4708-19. 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#. (2016) Divergent Clonal Selection Drives Medulloblastoma at Recurrence. Nature 529, 351–357 (* contributed equally, # co-corresponding authors). PMID: 26760213
2010 – 2015 (University of California, San Francisco)
  • 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. Nature Neuroscience 18(9): 1236-46. (* contributed equally, # co-corresponding authors) PMID: 26258683

 

  • 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. Nature Neuroscience 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. Nature Medicine (12): 1394-1396. PMID: 25401693

 

  • Huang X# and Jan LY#. (2014) Targeting potassium channels in cancer. Journal of Cell Biology 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 & Development 15; 26(16): 1780-96. (Cover Article) PMID: 22855790

 

  • 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
2004 – 2010 (Vanderbilt University)
  • 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. Journal of Visualized Experiments (44). pii: 2153. PMID: 20972404

 

  • Huang X, Ketova T, Litingtung Y, Chiang C. (2010) Isolation, enrichment and maintenance of medulloblastoma stem cells. Journal of Visualized Experiments (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

Editorial highlight:

Shh, choroid plexus growth in progress. Development. (2009) 136: e1502

 

  • 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. Developmental Dynamics 237(10): 3079-87 (* contributed equally) PMID: 18816854

 

  • 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. Developmental Dynamics 237(5): 1359-72. PMID: 18429041

 

  • 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

 

  • Huang X, Litingtung Y, Chiang C. (2007) Ectopic sonic hedgehog signaling impairs telencephalic dorsal midline development: implication for human holoprosencephaly. Human Molecular Genetics 16(12): 1454-68. PMID: 17468181

 

  • Oh S, Huang X, Chiang C. (2005) Specific requirements of sonic hedgehog signaling during oligodendrocyte development. Developmental Dynamics 234(3): 489-96. PMID: 15880651

Lab Socials

Lab Tour

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

 

Individuals interested in joining the lab as a graduate student must be admitted to the graduate program in the Department of Molecular Genetics at the University of Toronto

 

Undergraduate students can join the lab as long as they are enrolled in any department at a recognized university

Contact information

Dr. Xi Huang

Scientist

 

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)

Ms. Alicia Campbell

Administrative Assistant to Dr. Xi Huang

 

Peter Gilgan Centre for Research and Learning

686 Bay Street, 16.9801-U1

Toronto, ON M5G 0A4

(416) 813-7654 Ext: 309120