Dennis Mathew


Degrees
Ph.D. (2006), University of Massachusetts, Amherst, MA
M.Sc. (1998), M.S. University, Vadodara, India
B.Sc. (1996), University of Mumbai, Mumbai, India.

Positions and Employment
2014-         : Assistant Professor, Dept. Biology, University of Nevada, Reno, NV
2012-2014: Associate Research Scientist, Yale University, New Haven, CT
2006-2012: Postdoctoral Associate, Yale University, New Haven, CT
2000-2005: Research Assistant, University of Massachusetts, Amherst, MA

Personal Statement

The ability of an animal to detect, discriminate, and respond to odors underlies survival in the animal kingdom. Thus, the ability of a set of olfactory neurons to sample the environment and quickly and accurately transform the information into a behavioral response is critical to life. My investigation of an insect olfactory system spans multiple disciplines including neuroscience, behavior, physiology, molecular, and computational biology. My integrated approach to investigating olfactory circuit function led to my primary research interest exploring functional diversity among olfactory neurons and their respective contributions to behavior.

My fascination with neuroscience began during my first research experience as a graduate student. I was amazed by the intricate molecular mechanisms within neurons that allowed them to effectively communicate with one another as I investigated molecules enriched at the synapse. My Ph.D. studies investigated molecular mechanism underlying synapse plasticity at the Drosophila larval neuromuscular synapse.

During my post-doctoral research, I used behavioral and electrophysiological techniques to study olfaction in the Drosophila larva. Sophisticated olfactory function in the Drosophila larva is based on the activities of only 21 first order sensory neurons known as olfactory receptor neurons (ORNs). Each ORN expresses a single odor receptor protein that binds to odorants in the environment and converts chemical information into electrical signals. Electrical input from a single ORN is received by a second-order projection neuron (PN), which in turn relays information to higher olfactory centers in the brain. This information is modulated by the animal’s internal state that includes hunger, stress etc. and finally translated to effect a behavioral response. Because of my extensive training, I am an expert in assaying physiological responses of ORNs to odorants (information input), in exploring molecular mechanisms governing the modulation of olfactory information by the animal’s internal state (information processing), as well as in measuring behavioral responses of the animal to odorants (information output). Further, I’ve collaborated with physicists to study computational models of circuit function.

My Contributions to Science

Complete list of Published work in my Bibliography: http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/50465159/?sort=date&direction=ascending

Discovered Functional Diversity among Olfactory Receptor Neurons. I led the research that first screened the physiological response of 21 larval olfactory receptor neurons (ORNs) to a panel of ~500 odorants. I then identified most-effective ligands for 19 of the 21 ORNs. Using a number of behavioral paradigms, I showed that a strong physiological activity among ORNs do not always equate to a strong behavioral response in the larval. Our recent study confirms and extends this study to show that individual larval ORNs contribute differently to the composition of larval navigation. These and earlier results from studies that I collaborated on depart from the status quo because it considers an often overlooked aspect of sensory function – the diversity among individual neurons in a circuit. These results significantly impact our understanding of the functional organization of the larval olfactory system in particular, and the conclusions are likely applicable to other sensory circuits including those of humans. In a short period of time, the main study has already been cited 12 times. Several aspects of the study such as the discovery of most effective ligands for most larval ORNs have been cited by others (Boyle et al., 2013 Elife 2: e01120; Ebrahim et al., 2015 PLoS Biology 13: e1002318). The concept of functional diversity among neurons that was suggested in this study has also been cited by others (Hernandez-Nunez et al., 2015 Elife 4: 06225; Schulze et al., 2015 Elife 4: 06694).

  1. Kreher SA, Mathew D, Kim J, Carlson JR. “Translation of sensory input into behavioral output via an olfactory system” (2008) Neuron July 10; 59(1): 110-24
  2. Montague SA, Mathew D, Carlson JR. “Similar odorants elicit different behavioral and physiological responses, some supersustained” (2011) J Neurosci, May 25; 31(21): 7891-9
  3. Mathew D, Martelli C, Kelley-Swift E, Brusalis C, Gershow M, Samuel, A.D.T, Emonet T, Carlson JR. “Functional diversity among sensory receptors in a Drosophila olfactory circuit”, (2013) Proc Natl Acad Sci U S A. June 4; 110(23):E2134-43
  4. Newquist G, Novenschi A, Kohler D, Mathew D. “Differential contributions of olfactory receptor neurons in a Drosophila olfactory circuit”, eNeuro  DOI:10.1523/ENEURO.0045-16.2016 (2016).

Developed a Novel Method for Tracking Animal Navigation. Together with colleagues, we developed a novel behavioral paradigm that allows tracking of the navigational trajectories of individual larvae. We continue to use this paradigm, in combination with custom written machine-vision algorithms, to assess and quantify navigational decision making strategies of Drosophila larvae in response to a wide variety of odorants. This methodology is unlike any other contemporary behavioral paradigm because the flexibility and accuracy with which this system combines olfactory stimulation to freely moving animals along with machine-vision analysis that is sensitive to time-varying position and posture of each animal, enables a detailed analysis of navigational behavior with new levels of precision. This method has already resulted in three publications for the PI and it continues to provide opportunities to test a number of critical hypotheses relevant to sensory neuroscience including ones proposed in the current proposal.

  1. Gershow M, Berck M, Mathew D, Luo L, Kane EA, Carlson JR, Samuel ADT. “Controlling airborne chemical cues for studying navigation in small animals”, (2012) Nature Methods, Jan 15, doi:10.1038/nmeth.1853
  2. Mathew D, Martelli C, Kelley-Swift E, Brusalis C, Gershow M, Samuel, A.D.T, Emonet T, Carlson JR. “Functional diversity among sensory receptors in a Drosophila olfactory circuit”, (2013) Proc Natl Acad Sci U S A. June 4; 110(23):E2134-43

Described Rapid Recycling of Fasciclin-II at a Synapse. I used the glutamatergic Drosophila larval neuromuscular junction to study the synaptic regulation of Fas-II by Amphiphysin (dAmph). I developed an in vivo Fas-II immunocapture protocol to show that the level of external Fas-II is decreased in damph mutants. I was able to show that reincorporation of Fas-II molecules into the cell surface was severely inhibited in damph mutants via a SNARe dependent mechanism. This contribution was unique for two reasons: (i) because it challenged the notion that synaptic Amphiphysin is involved exclusively in endocytosis and suggested a novel role for this protein in postsynaptic exocytosis; and (ii) it provided a mechanism for the rapid recycling of a cell adhesion molecule (Fas-II) at the synapse. This mechanism is essential not only for developmental aspects of the nervous system but is also a basic element in the acquisition and maintenance of memories. This work was quoted by 28 publications including a study by another group that related this work to the L1 Cell adhesion molecule in a mammalian hippocampus (Itoh et al., 2005 Mol Cell Neurosci 29: 245-9).

  1. Mathew D, Popescu A and Budnik V. “Drosophila amphiphysin functions during synaptic Fasciclin II membrane cycling” (2003) J Neurosci. Nov 19; 23(33): 10710-6.
  2. Packard M, Mathew D, Budnik V. “FASt remodeling of synapses in Drosophila” (2003) Curr Opin Neurobiol Oct 13; (5): 527-34

Discovered a Non-Canonical Wnt-Signaling Pathway. I made the significant discovery of a non-canonical Wnt-signaling pathway, in which the Wnt receptor DFrizzled-2 (DFz-2) itself was endocytosed in the postsynapse of the Drosophila larval neuromuscular junction, its C-terminus cleaved, and the C-terminal fragment imported into the nucleus to regulate the synthesis of postsynaptic proteins. This study was unique because: (i) it provided the first evidence for a non-canonical pathway for Wnt-signaling; and (ii) it revealed an important and previously uncharacterized role for well-known early developmental genes in synapse differentiation and plasticity. The main study that was published in the Journal, ‘Science’ has been cited 68 times. The importance of this study was highlighted in a perspective article provided in the same issue of the journal (Martinez-Arias, 2005 Science 310: 1284-85). According to the perspective, “This cleavage of DFz-2 represents a novel modality of Wnt signaling, a pervasive pathway in animal development”. This discovery formed the foundation for the study of a novel mechanism by which ribonucleoprotein particles are assembled in the nucleus and exported to the cytoplasm for localized translation of mRNAs at postsynaptic sites (Speese et al., 2012 Cell 149: 832-46).

  1. Mathew D, Ataman B, Chen J, Zhang Y, Cumberledge S and Budnik V. “Novel mechanism of wingless signaling at synapses via DFrizzled2 cleavage and nuclear import” (2005) Science Nov 25; 310 (5752): 1344-7.
  2. Packard M, Mathew D and Budnik V. “Wnts and TGF beta in synaptogenesis: old friends signalling at new places” (2003) Nat Rev Neurosci. Feb 4; (2): 113-20.
  3. Ataman B, Ashley J, Gorczyca D, Gorczyca M, Mathew D, Wichmann C, Sigrist SJ and Budnik V. “Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP” (2006) Proc Natl Acad Sci U S A. May 16; 103(20): 7841-6