About

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-present: 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

Curriculum Vitae_Dennis Mathew

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. 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:  https://www.ncbi.nlm.nih.gov/myncbi/browse/collection/50465159/?sort=date&direction=descending

The demonstration of rapid recycling of Fasciclin-II at the neuromuscular 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 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 has been cited by 51 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, Budnik V (2003) Drosophila amphiphysin functions during synaptic Fasciclin II membrane cycling. The Journal of neuroscience : the official journal of the Society for Neuroscience 23:10710-10716.
  2. Packard M, Mathew D, Budnik V (2003) FASt remodeling of synapses in Drosophila. Current opinion in neurobiology 13:527-534

 

The demonstration of a non-canonical Wnt-signaling pathway. I discovered a non-canonical Wnt-signaling pathway, in which the Wnt receptor DFrizzled-2 (DFz-2) itself was endocytosed at the postsynaptic membrane 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 171 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, Budnik V (2005) Wingless signaling at synapses is through cleavage and nuclear import of receptor DFrizzled2. Science 310:1344-1347.
  2. Ataman B, Ashley J, Gorczyca D, Gorczyca M, Mathew D, Wichmann C, Sigrist SJ, Budnik V (2006) Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP. PNAS 103:7841-7846.
  3. Packard M, Mathew D, Budnik V (2003) Wnts and TGF beta in synaptogenesis: old friends signalling at new places. Nature reviews Neuroscience 4:113-12

 

The development of a novel method to track larval navigation. Together with colleagues at Yale and Harvard Universities, I 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, enable a detailed analysis of navigational behavior with new levels of precision. This method has already resulted in five 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. We have now added an optogentics module to this behavioral assay and the technique of optogenetically targeting individual olfactory neurons was published as a methods paper in JoVE in 2018.

  1. Mathew D, Martelli C, Kelley-Swift E, Brusalis C, Gershow M, Samuel AD, Emonet T, Carlson JR (2013) Functional diversity among sensory receptors in a Drosophila olfactory circuit. PNAS 110:E2134-2143.
  2. Gershow M, Berck M, Mathew D, Luo L, Kane EA, Carlson JR, Samuel AD (2012) Controlling airborne cues to study small animal navigation. Nature methods 9:290-296.
  3. Clark DA, Kohler D, Mathis A, Slankster E, Kafle S, Odell SR, Mathew D (2018a) Tracking Drosophila Larval Behavior in Response to Optogenetic Stimulation of Olfactory Neurons. Journal of visualized experiments : JoVE (133).

 

The demonstration of Functional Diversity among Olfactory Receptor Neurons. I led the research that first screened the physiological responses 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 does 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 studies are important because they consider an often overlooked aspect of sensory function – the diversity among individual neurons in a circuit. The results of these studies 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 published in 2013 has been cited 62 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. Mathew D, Martelli C, Kelley-Swift E, Brusalis C, Gershow M, Samuel AD, Emonet T, Carlson JR (2013) Functional diversity among sensory receptors in a Drosophila olfactory circuit. PNAS 110:E2134-2143.
  2. Montague SA, Mathew D, Carlson JR (2011) Similar odorants elicit different behavioral and physiological responses, some supersustained. The Journal of neuroscience : the official journal of the Society for Neuroscience 31:7891-7899.
  3. Clark DA, Odell SR, Armstrong JM, Turcotte M, Kohler D, Mathis A, Schmidt DR, Mathew D (2018) Behavior Responses to Chemical and Optogenetic Stimuli in Drosophila Larvae. Frontiers in behavioral neuroscience 12:324.
  4. Newquist G, Novenschi A, Kohler D, Mathew D (2016) Differential Contributions of Olfactory Receptor Neurons in a Drosophila Olfactory Circuit. Eneuro 3 e0045-16:1-15.