Research

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Maxwell G. Heiman, PhD

Maxwell G. Heiman
Program:
Neurobiology Program
Department:
Medicine Research
Division
Genetics and Genomics Research
Hospital Title:
Principal Investigator
Academic Title:
Assistant Professor of Genetics, Harvard Medical School
Research Focus Area:
Genetics
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Research Overview

The human brain is the most amazing self-assembling machine in the world. Our interest is in understanding how the 100 billion neurons and 100 billion glia that compose our brains are able to acquire the necessary shapes and make the necessary cell-cell contacts to give rise to human consciousness. To identify the basis of neuronal shape and connectivity at a fundamental level, we have turned to the simple model system of the roundworm C. elegans, a nematode whose entire nervous system contains only 302 neurons. Remarkably, each of these neurons acquires the same shape and makes the same cell-cell contacts in every individual. Thus, because this nervous system is "genetically hard-wired," it is straightforward to isolate mutants that disrupt wiring and then to identify the relevant genes. We have focused, for a start, on the major sense organ of C. elegans, called the amphid. The amphid contains 12 sensory neurons ensheathed by two glial cells. The neurons extend unbranched dendrites to the tip of the nose. We have characterized an unusual mechanism by which these dendrites extend, and have identified a pair of secreted matrix proteins--similar to those involved in sperm-egg adhesion--which are required to define the contact site at the nose where the dendrites attach. In ongoing work, we seek to characterize the mechanism by which the amphid contact site is specified, as well as how distinct contact sites at the nose tip are specified to collectively determine the sensory anatomy of this simple organism. By identifying how neurons get their shapes and make the right contacts in this model system, we aim to establish an intellectual framework that will help us understand how our own brain's far more complex anatomy is encoded.

About Maxwell G. Heiman

Max Heiman received a BS in Biology from Yale University in 1997, studying homeobox gene regulation in the laboratory of Frank Ruddle. In 2003, he received a PhD in Biochemistry from the University of California, San Francisco. There, he worked in the laboratory of Peter Walter and identified factors that regulate cell-cell fusion, using yeast mating as a model genetic system. He then conducted postdoctoral studies at Rockefeller University in the laboratory of Shai Shaham, using C. elegans as a model system in which to characterize neuronal and glial development. Heiman's general interests are in the self-assembly of complex biological structures, ranging in scale from extracellular matrix fibrils to the complete nervous system. He has been a fellow of the Howard Hughes Medical Institute and the Jane Coffin Childs Fund.

Publications

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  1. Nechipurenko IV, Olivier-Mason A, Kazatskaya A, Kennedy J, McLachlan IG, Heiman MG, Blacque OE, Sengupta P. A Conserved Role for Girdin in Basal Body Positioning and Ciliogenesis. Dev Cell. 2016 Sep 12; 38(5):493-506.
  2. Yip ZC, Heiman MG. Duplication of a Single Neuron in C. elegans Reveals a Pathway for Dendrite Tiling by Mutual Repulsion. Cell Rep. 2016 Jun 7; 15(10):2109-17.
  3. Gilleland CL, Falls AT, Noraky J, Heiman MG, Yanik MF. Computer-Assisted Transgenesis of Caenorhabditis elegans for Deep Phenotyping. Genetics. 2015 Sep; 201(1):39-46.
  4. Mizeracka K, Heiman MG. The many glia of a tiny nematode: studying glial diversity using Caenorhabditis elegans. Wiley Interdiscip Rev Dev Biol. 2015 Mar-Apr; 4(2):151-60.
  5. McLachlan IG, Heiman MG. Shaping dendrites with machinery borrowed from epithelia. Curr Opin Neurobiol. 2013 Dec; 23(6):1005-10.
  6. Heiman MG, Pallanck L. Neurons at the extremes of cell biology. Mol Biol Cell. 2011 Mar 15; 22(6):721.
  7. Aguilar PS, Heiman MG, Walther TC, Engel A, Schwudke D, Gushwa N, Kurzchalia T, Walter P. Structure of sterol aliphatic chains affects yeast cell shape and cell fusion during mating. Proc Natl Acad Sci U S A. 2010 Mar 2; 107(9):4170-5.
  8. Heiman MG, Shaham S. Ancestral roles of glia suggested by the nervous system of Caenorhabditis elegans. Neuron Glia Biol. 2007 Feb; 3(1):55-61.
  9. Heiman MG, Walter P. Prm1p, a pheromone-regulated multispanning membrane protein, facilitates plasma membrane fusion during yeast mating. J Cell Biol. 2000 Oct 30; 151(3):719-30.
  10. Heiman MG, Shaham S. DEX-1 and DYF-7 establish sensory dendrite length by anchoring dendritic tips during cell migration. Cell. 2009 Apr 17; 137(2):344-55.
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  12. Heiman MG, Engel A, Walter P. The Golgi-resident protease Kex2 acts in conjunction with Prm1 to facilitate cell fusion during yeast mating. J Cell Biol. 2007 Jan 15; 176(2):209-22.
  13. Heiman MG, Shaham S. Twigs into branches: how a filopodium becomes a dendrite. Curr Opin Neurobiol. 2010 Feb; 20(1):86-91.
  14. Kelley M, Yochem J, Krieg M, Calixto A, Heiman MG, Kuzmanov A, Meli V, Chalfie M, Goodman MB, Shaham S, Frand A, Fay DS. FBN-1, a fibrillin-related protein, is required for resistance of the epidermis to mechanical deformation during C. elegans embryogenesis. Elife. 2015 Mar 23; 4.
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