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Alvin Kho, PhD

Alvin Kho, PhD
Program:
Computational Health Informatics Program (CHIP)
Department:
Medicine Research
Hospital Title:
Associate Scientific Researcher
Academic Title:
Instructor in Pediatrics, Harvard Medical School
Research Focus Area:
BioinformaticsMulti-scale Mathematical Models of Developing and Pathogenic SystemsFetal programmingSystems Analysis
Contact:
617-355-6393
Contact Via Email
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Research Overview

In his research, Alvin Kho builds mathematical models of developing biological systems to identify developmental programs that underwrite pathobiology in these systems with the aim of translating this knowledge into clinically-relevant endpoints. He has investigated transcriptomes of the developing central nervous system (PMID:15075291), skeletal muscle (PMID:21337346) and lung (PMID:16800721, 19815808, 18664640) and identified molecular correlates associated with (normal) organ-specific function and disease traits in these systems. Recently, he has focused on the role of in utero exposures (e.g., vitamin D, corticosteroids) in the pathobiology of chronic disease that occur later in life such as asthma and COPD (PMID:22983352, 24188128, 24668408).

Publications

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  1. Zhang H, Kho AT, Wu Q, Halayko AJ, Limbert Rempel K, Chase RP, Sweezey NB, Weiss ST, Kaplan F. CRISPLD2 (LGL1) inhibits proinflammatory mediators in human fetal, adult, and COPD lung fibroblasts and epithelial cells. Physiol Rep. 2016 Sep; 4(17).
  2. Beauchemin KJ, Wells JM, Kho AT, Philip VM, Kamir D, Kohane IS, Graber JH, Bult CJ. Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development. PeerJ. 2016; 4:e2318.
  3. Kho AT, Sharma S, Davis JS, Spina J, Howard D, McEnroy K, Moore K, Sylvia J, Qiu W, Weiss ST, Tantisira KG. Circulating MicroRNAs: Association with Lung Function in Asthma. PLoS One. 2016; 11(6):e0157998.
  4. Kho AT, Chhabra D, Sharma S, Qiu W, Carey VJ, Gaedigk R, Vyhlidal CA, Leeder JS, Tantisira KG, Weiss ST. Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome. Am J Respir Cell Mol Biol. 2016 Jun; 54(6):814-21.
  5. Oh DY, Dowling DJ, Ahmed S, Choi H, Brightman S, Bergelson I, Berger ST, Sauld JF, Pettengill M, Kho AT, Pollack HJ, Steen H, Levy O. Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures. Mol Cell Proteomics. 2016 Jun; 15(6):1877-94.
  6. Prilutsky D, Kho AT, Palmer NP, Bhakar AL, Smedemark-Margulies N, Kong SW, Margulies DM, Bear MF, Kohane IS. Gene expression analysis in Fmr1KO mice identifies an immunological signature in brain tissue and mGluR5-related signaling in primary neuronal cultures. Mol Autism. 2015; 6:66.
  7. Haas DM, Lai D, Sharma S, Then J, Kho A, Flockhart DA, Tantisira K, Foroud T. Steroid Pathway Genes and Neonatal Respiratory Distress After Betamethasone Use in Anticipated Preterm Birth. Reprod Sci. 2016 May; 23(5):680-6.
  8. Park JA, Kim JH, Bi D, Mitchel JA, Qazvini NT, Tantisira K, Park CY, McGill M, Kim SH, Gweon B, Notbohm J, Steward R, Burger S, Randell SH, Kho AT, Tambe DT, Hardin C, Shore SA, Israel E, Weitz DA, Tschumperlin DJ, Henske EP, Weiss ST, Manning ML, Butler JP, Drazen JM, Fredberg JJ. Unjamming and cell shape in the asthmatic airway epithelium. Nat Mater. 2015 Oct; 14(10):1040-8.
  9. Sharma S, Kho AT, Chhabra D, Qiu W, Gaedigk R, Vyhlidal CA, Leeder JS, Barraza-Villarreal A, London SJ, Gilliland F, Raby BA, Weiss ST, Tantisira KG. Glucocorticoid genes and the developmental origins of asthma susceptibility and treatment response. Am J Respir Cell Mol Biol. 2015 May; 52(5):543-53.
  10. Chhabra D, Sharma S, Kho AT, Gaedigk R, Vyhlidal CA, Leeder JS, Morrow J, Carey VJ, Weiss ST, Tantisira KG, DeMeo DL. Fetal lung and placental methylation is associated with in utero nicotine exposure. Epigenetics. 2014 Nov; 9(11):1473-84.
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  12. Crosslin DR, Carrell DS, Burt A, Kim DS, Underwood JG, Hanna DS, Comstock BA, Baldwin E, de Andrade M, Kullo IJ, Tromp G, Kuivaniemi H, Borthwick KM, McCarty CA, Peissig PL, Doheny KF, Pugh E, Kho A, Pacheco J, Hayes MG, Ritchie MD, Verma SS, Armstrong G, Stallings S, Denny JC, Carroll RJ, Crawford DC, Crane PK, Mukherjee S, Bottinger E, Li R, Keating B, Mirel DB, Carlson CS, Harley JB, Larson EB, Jarvik GP. Genetic variation in the HLA region is associated with susceptibility to herpes zoster. Genes Immun. 2015 Jan-Feb; 16(1):1-7.
  13. Sharma S, Chhabra D, Kho AT, Hayden LP, Tantisira KG, Weiss ST. The genomic origins of asthma. Thorax. 2014 May; 69(5):481-7.
  14. Kho AT, Sharma S, Qiu W, Gaedigk R, Klanderman B, Niu S, Anderson C, Leeder JS, Weiss ST, Tantisira KG. Vitamin D related genes in lung development and asthma pathogenesis. BMC Med Genomics. 2013 Nov 05; 6:47.
  15. Kho AT, Liu K, Visner G, Martin T, Boudreault F. Identification of dedifferentiation and redevelopment phases during postpneumonectomy lung growth. Am J Physiol Lung Cell Mol Physiol. 2013 Oct 15; 305(8):L542-54.
  16. Patel NR, Bole M, Chen C, Hardin CC, Kho AT, Mih J, Deng L, Butler J, Tschumperlin D, Fredberg JJ, Krishnan R, Koziel H. Cell elasticity determines macrophage function. PLoS One. 2012; 7(9):e41024.
  17. Carpe N, Mandeville I, Kho AT, Qiu W, Martin JG, Tantisira KG, Raby BA, Weiss ST, Kaplan F. Maternal allergen exposure reprograms the developmental lung transcriptome in atopic and normoresponsive rat pups. Am J Physiol Lung Cell Mol Physiol. 2012 Nov 15; 303(10):L899-911.
  18. Melén E, Kho AT, Sharma S, Gaedigk R, Leeder JS, Mariani TJ, Carey VJ, Weiss ST, Tantisira KG. Expression analysis of asthma candidate genes during human and murine lung development. Respir Res. 2011 Jun 23; 12:86.
  19. Liu F, Mih JD, Shea BS, Kho AT, Sharif AS, Tager AM, Tschumperlin DJ. Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression. J Cell Biol. 2010 Aug 23; 190(4):693-706.
  20. Carpe N, Mandeville I, Ribeiro L, Ponton A, Martin JG, Kho AT, Chu JH, Tantisira K, Weiss ST, Raby BA, Kaplan F. Genetic influences on asthma susceptibility in the developing lung. Am J Respir Cell Mol Biol. 2010 Dec; 43(6):720-30.
  21. Kojic N, Chung E, Kho AT, Park JA, Huang A, So PT, Tschumperlin DJ. An EGFR autocrine loop encodes a slow-reacting but dominant mode of mechanotransduction in a polarized epithelium. FASEB J. 2010 May; 24(5):1604-15.
  22. Kho AT, Bhattacharya S, Tantisira KG, Carey VJ, Gaedigk R, Leeder JS, Kohane IS, Weiss ST, Mariani TJ. Transcriptomic analysis of human lung development. Am J Respir Crit Care Med. 2010 Jan 1; 181(1):54-63.
  23. Du R, Tantisira K, Carey V, Bhattacharya S, Metje S, Kho AT, Klanderman BJ, Gaedigk R, Lazarus R, Mariani TJ, Leeder JS, Weiss ST. Platform dependence of inference on gene-wise and gene-set involvement in human lung development. BMC Bioinformatics. 2009 Jun 19; 10:189.
  24. Arashiro P, Eisenberg I, Kho AT, Cerqueira AM, Canovas M, Silva HC, Pavanello RC, Verjovski-Almeida S, Kunkel LM, Zatz M. Transcriptional regulation differs in affected facioscapulohumeral muscular dystrophy patients compared to asymptomatic related carriers. Proc Natl Acad Sci U S A. 2009 Apr 14; 106(15):6220-5.
  25. Kho AT, Bhattacharya S, Mecham BH, Hong J, Kohane IS, Mariani TJ. Expression profiles of the mouse lung identify a molecular signature of time-to-birth. Am J Respir Cell Mol Biol. 2009 Jan; 40(1):47-57.
  26. Gobezie R, Kho A, Krastins B, Sarracino DA, Thornhill TS, Chase M, Millett PJ, Lee DM. High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis. Arthritis Res Ther. 2007; 9(2):R36.
  27. Schüller U, Kho AT, Zhao Q, Ma Q, Rowitch DH. Cerebellar 'transcriptome' reveals cell-type and stage-specific expression during postnatal development and tumorigenesis. Mol Cell Neurosci. 2006 Nov; 33(3):247-59.
  28. Hung KE, Kho AT, Sarracino D, Richard LG, Krastins B, Forrester S, Haab BB, Kohane IS, Kucherlapati R. Mass spectrometry-based study of the plasma proteome in a mouse intestinal tumor model. J Proteome Res. 2006 Aug; 5(8):1866-78.
  29. Cerletti M, Molloy MJ, Tomczak KK, Yoon S, Ramoni MF, Kho AT, Beggs AH, Gussoni E. Melanoma cell adhesion molecule is a novel marker for human fetal myogenic cells and affects myoblast fusion. J Cell Sci. 2006 Aug 1; 119(Pt 15):3117-27.
  30. Liu H, Kho AT, Kohane IS, Sun Y. Predicting survival within the lung cancer histopathological hierarchy using a multi-scale genomic model of development. PLoS Med. 2006 Jul; 3(7):e232.
  31. Gazda HT, Kho AT, Sanoudou D, Zaucha JM, Kohane IS, Sieff CA, Beggs AH. Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemia. Stem Cells. 2006 Sep; 24(9):2034-44.
  32. Kho AT, Kang PB, Kohane IS, Kunkel LM. Transcriptome-scale similarities between mouse and human skeletal muscles with normal and myopathic phenotypes. BMC Musculoskelet Disord. 2006 Mar 07; 7:23.
  33. Cerletti M, Molloy MJ, Tomczak KK, Yoon S, Ramoni MF, Kho AT, Beggs AH and Gussoni E. Melanoma Cell Adhesion Molecule is a novel marker for human fetal myogenic cells and affects myoblast fusion. J Cell Sci. 119, 3117-27, 2006. 2006; 119(Pt 15):3117-27.
  34. Gazda HT, Kho AT, Sanoudou D, JM, Kohane IS, Sieff CA, Beggs AH. Alteration of ribosomal protein gene expression, transcription, apoptosis and cancer pathways in Diamond-Blackfan anemia. Stem Cells. 2006; 24(9):2033-44.
  35. Haslett JN, Kang PB, Han M, Kho AT, Sanoudou D, Volinski JM, Beggs AH, Kohane IS, Kunkel LM. The influence of muscle type and dystrophin deficiency on murine expression profiles. Mamm Genome. 2005 Oct; 16(10):739-48.
  36. Liadaki K, Kho AT, Sanoudou D, Schienda J, Flint A, Beggs AH, Kohane IS, Kunkel LM. Side population cells isolated from different tissues share transcriptome signatures and express tissue-specific markers. Exp Cell Res. 2005 Feb 15; 303(2):360-74.
  37. Ligon KL, Alberta JA, Kho AT, Weiss J, Kwaan MR, Nutt CL, Louis DN, Stiles CD, Rowitch DH. The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas. J Neuropathol Exp Neurol. 2004 May; 63(5):499-509.
  38. Sanoudou D, Frieden LA, Haslett JN, Kho AT, Greenberg SA, Kohane IS, Kunkel LM, Beggs AH. Molecular classification of nemaline myopathies: "nontyping" specimens exhibit unique patterns of gene expression. Neurobiol Dis. 2004 Apr; 15(3):590-600.
  39. Kho AT, Zhao Q, Cai Z, Butte AJ, Kim JY, Pomeroy SL, Rowitch DH, Kohane IS. Conserved mechanisms across development and tumorigenesis revealed by a mouse development perspective of human cancers. Genes Dev. 2004 Mar 15; 18(6):629-40.
  40. Lennon NJ, Kho A, Bacskai BJ, Perlmutter SL, Hyman BT, Brown RH. Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing. J Biol Chem. 2003 Dec 12; 278(50):50466-73.
  41. Haslett JN, Sanoudou D, Kho AT, Han M, Bennett RR, Kohane IS, Beggs AH, Kunkel LM. Gene expression profiling of Duchenne muscular dystrophy skeletal muscle. Neurogenetics. 2003 Aug; 4(4):163-71.
  42. Sanoudou D, Haslett JN, Kho AT, Guo S, Gazda HT, Greenberg SA, Lidov HG, Kohane IS, Kunkel LM, Beggs AH. Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle. Proc Natl Acad Sci U S A. 2003 Apr 15; 100(8):4666-71.
  43. Haslett JN, Sanoudou D, Kho AT, Bennett RR, Greenberg SA, Kohane IS, Beggs AH, Kunkel LM. Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle. Proc Natl Acad Sci U S A. 2002 Nov 12; 99(23):15000-5.
  44. Isaac S. Kohane, Alvin T. Kho, Atul J. Butte . Microarrays for an Integrative Genomics Microarrays for an Integrative Genomics. 2002; 326.
  45. Zhao Q, Kho A, Kenney AM, Yuk Di DI, Kohane I, Rowitch DH. Identification of genes expressed with temporal-spatial restriction to developing cerebellar neuron precursors by a functional genomic approach. Proc Natl Acad Sci U S A. 2002 Apr 16; 99(8):5704-9.
  46. Tsien CL, Libermann TA, Gu X, Kho A, Kohane IS. CHIP TUNER: a web tool for evidence-based noise reduction in gene discovery. Proc AMIA Symp. 2002; 810-4.
  47. Katsoulakis MA, Kho AT (3) 265-290, 2001. Stochastic mean curvature flows: Asymptotic derivation, level set formulation and numerics. Interfaces and Free Boundaries. 2001; 3:265-90.
  48. Alvin Thong-Juak Kho. Multi-scale analysis for microscropic models in materials science and cell biology. 2000.
  49. Ning M, Sarracino DA, Kho AT, Guo S, Lee SR, Krastins B, Buonanno FS, Vizcaíno JA, Orchard S, McMullin D, Wang X, Lo EH. Proteomic temporal profile of human brain endothelium after oxidative stress. Stroke. 2011 Jan; 42(1):37-43.
  50. Frank NY, Kho AT, Schatton T, Murphy GF, Molloy MJ, Zhan Q, Ramoni MF, Frank MH, Kohane IS, Gussoni E. Regulation of myogenic progenitor proliferation in human fetal skeletal muscle by BMP4 and its antagonist Gremlin. J Cell Biol. 2006 Oct 9; 175(1):99-110.
  51. Alexander MS, Kawahara G, Kho AT, Howell MH, Pusack TJ, Myers JA, Montanaro F, Zon LI, Guyon JR, Kunkel LM. Isolation and transcriptome analysis of adult zebrafish cells enriched for skeletal muscle progenitors. Muscle Nerve. 2011 May; 43(5):741-50.
  52. Schüller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG, Huillard E, Sun T, Ligon AH, Qian Y, Ma Q, Alvarez-Buylla A, McMahon AP, Rowitch DH, Ligon KL. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell. 2008 Aug 12; 14(2):123-34.
  53. Kang PB, Kho AT, Sanoudou D, Haslett JN, Dow CP, Han M, Blasko JM, Lidov HG, Beggs AH, Kunkel LM. Variations in gene expression among different types of human skeletal muscle. Muscle Nerve. 2005 Oct; 32(4):483-91.
  54. Alexander MS, Kawahara G, Motohashi N, Casar JC, Eisenberg I, Myers JA, Gasperini MJ, Estrella EA, Kho AT, Mitsuhashi S, Shapiro F, Kang PB, Kunkel LM. MicroRNA-199a is induced in dystrophic muscle and affects WNT signaling, cell proliferation, and myogenic differentiation. Cell Death Differ. 2013 Sep; 20(9):1194-208.
  55. McGeachie MJ, Yates KP, Zhou X, Guo F, Sternberg AL, Van Natta ML, Wise RA, Szefler SJ, Sharma S, Kho AT, Cho MH, Croteau-Chonka DC, Castaldi PJ, Jain G, Sanyal A, Zhan Y, Lajoie BR, Dekker J, Stamatoyannopoulos J, Covar RA, Zeiger RS, Adkinson NF, Williams PV, Kelly HW, Grasemann H, Vonk JM, Koppelman GH, Postma DS, Raby BA, Houston I, Lu Q, Fuhlbrigge AL, Tantisira KG, Silverman EK, Tonascia J, Weiss ST, Strunk RC. Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma. N Engl J Med. 2016 May 12; 374(19):1842-52.
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