Muscarinic receptor antagonism as a novel mechanism for sensory nerve repair (CIHR)

Diabetic sensory neuropathy and chemotherapy-induced peripheral neuropathy (CIPN) are neurodegenerative diseases characterized by loss of nerve fibres in the skin. Both diseases cause significant pain and eventually lead to sensory loss. The impact of these diseases on human health is enormously damaging and there are no therapies. Our recent work has uncovered an endogenous signalling pathway in neurons that negatively modulates nerve fibre growth of sensory neurons. The neurotransmitter, acetylcholine, is produced by sensory neurons and skin cells and activates the muscarinic receptor. Inhibiting the function of the receptor in sensory neurons using selective drugs or genetically removing the gene significantly increases nerve fibre growth.
We propose a “cholinergic constraint hypothesis” describing a role for acetylcholine in restricting the growth of nerves within the skin.

The general objectives are:

1. To suppress the muscarinic receptor pathway to repair nerve endings damaged by diabetes or anti-cancer agents.
2. To determine the mechanism whereby receptor blockade enhances nerve growth with a focus on a role in the control of calcium signalling and mitochondrial function.

Impact statement

The proposed studies have strong translational potential if successful. Our work with topical delivery of muscarinic blocking drugs (already USFDA-approved for another indication) has progressed to a point where one small phase 2 clinical trial is complete and additional studies are envisaged to be completed by February 2022 for the treatment of diabetic neuropathy. The USFDA has awarded our novel topical formulation an IND with fast track designation. A company, WinSanTor, Inc., has been set up and will oversee the delivery of this plan. This proposal, if funded, will enable the work to broaden in scope and permit this therapeutic approach to be performed in a wide range of distal dying back neurodegenerative diseases.

Correcting aberrant axonal bioenergetics to drive nerve repair in neurological disease.

(Ben Gurion Univ/St. Boniface Foundation) Defects in neuronal energy supply occur in several neurological diseases, including Alzheimer’s disease and neuropathies of the peripheral nervous system (PNS). We recently showed that antimuscarinic drugs enhance mitochondrial function and drive nerve repair in a variety of neuropathic diseases of the PNS, including HIV neuropathy and diabetic neuropathy. These drugs work by blocking, through an unknown mechanism, an endogenous cholinergic pathway that is inhibitory to mitochondrial function and axonal outgrowth. Drugs with selective or specific antagonism of the muscarinic acetylcholine type 1 receptor (M1R) were most efficacious.

Hypothesis

We will test if suppression of M1R signalling leads to enhanced Ca2+ signalling and activation of the Ca2+/calmodulin-dependent protein kinase kinase  (CaMKK and AMP-activated protein kinase (AMPK) pathway that augments mitochondrial function at multiple levels to drive axonal outgrowth and survival.

Objectives

In vitro studies using adult sensory neurons will aim to identify Ca2+ channels, for example, TRPM3, required for raised Ca2+ subsequent to antimuscarinic treatment. Intracellular Ca2+ and mitochondrial function will be imaged simultaneously and in parallel-energy status will be determined using real-time imaging with ATP biosensors (ATeam constructs). Complementary studies will fully characterize mitochondrial function using the Seahorse XF24 analyzer. Previous work in diabetic humans and animals models reveals decreased sensory innervation of the cornea. Thus, non-invasive in vivo confocal imaging of the cornea will be used to study ATP levels in sensory nerve endings derived from the trigeminal ganglion of mice with neuronal-specific Thy1.2-driven ATeam expression. In vitro and in vivo studies with sensory neurons will be performed using normal and type 1 diabetic mice (mice will be made diabetic with streptozotocin) and the impact of the diabetic state on bioenergetics, e.g. [ATP], in live axons will be determined for the first time. Antimuscarinic drugs will be applied topically to the cornea to attempt to reverse bioenergetic deficits and stimulate nerve growth. For the in vitro work, control studies will be performed with sensory neurons derived from M1R knockout mice to prove the involvement of M1R.

Specific Aims

AIM 1 Mechanism of antimuscarinic drug-induced enhancement of mitochondrial function via Ca2+ mobilization in cultured adult neurons. 

AIM 2 Non-invasive confocal in vivo imaging to determine the mechanism of antimuscarinic drug action in sensory fibres of the cornea of diabetic mice.

Impact

These comprehensive studies will directly link for the first time sub-optimal energy production associated with diabetes, with impaired axonal regeneration in neuropathy, and will identify the mechanism of action of antimuscarinic drugs. Commercialization is underway with these drugs for the treatment of peripheral neuropathy. Phase 2 trials in persons with type 2 diabetes are planned. These proposed studies will elevate our understanding of the mechanism of drug action and, hopefully, will accelerate translation to the bedside.

Energy failure in nerve fibres: its detection and therapeutic reversal in neurological disease. (Bank of Montreal)

Background in neurological diseases of the central and peripheral nervous systems (CNS and PNS) studies reveal that impaired mitochondrial function leads to the neurodegeneration of nerve cells and their circuits (dendrites, axons and synapses) (Chowdhury, Smith et al. 2013, Cai and Tammineni 2016). Disease processes such as Alzheimer’s and diabetes directly impact mitochondrial physiology to cause a down-regulation in the ability of the organelle to supply energy (in the form of ATP). Failure of energy supply leads to impaired electrical excitability and sup-optimal ion homeostasis in nerve cells that triggers cell death and degeneration (Bennett, Doyle et al. 2014). The degeneration of synapses and nerve endings leads to loss of connectivity in the nervous system and drives impaired cognition and sensation (Cashman and Hoke 2015). At present, there are no therapies that can reverse these neurodegenerative processes.

Specific Aims

We recently published work in the Journal of Clinical Investigation showing that antimuscarinic drugs can be utilized to augment mitochondrial function and drive nerve repair (Calcutt, Smith et al. 2017). The main purpose of the current work is to reveal the mechanism of action of these drugs using an in vivo approach that is non-invasive. Mouse models of Alzheimer’s or peripheral neuropathy will be utilized and the ability of antimuscarinic drugs to reverse nerve damage will be determined while live imaging the same nerve fibres. New optical techniques permit real-time imaging of nerve fibres in the cornea (Tavakoli, Petropoulos et al. 2013). It is known in human disease and related animal models that the nerve fibres innervating the cornea undergo neurodegeneration (Chen, Frizzi et al. 2013, De Clerck, Schouten et al. 2015). Therefore, we hypothesize that during neurological disease the nerve fibres in the cornea will degenerate and this will be due to mitochondrial dysfunction driven by stressors related to diabetes or Alzheimer’s. There are the following specific aims:

• Aim 1 (year 1) – Live imaging of the corneal nerve fibres to reveal degeneration of fibres in animal models of CNS and PNS disease.
• Aim 2 (years 2-3) – In vivo quantification of abnormalities in mitochondrial function and energy supply in nerve fibres.
• Aim 3 (years 4-5) – Use antimuscarinic drugs for therapy in animal models of Alzheimer’s and type 1 diabetes and determine if mitochondrial dysfunction and fibre loss can be reversed.

SPOR Network in diabetes and its related complications.

Background

Individuals with diabetes, representing ~10% of Canadians, are deeply concerned about their risk of developing blindness, limb amputations, kidney and heart failure, and hypoglycemia. Among the most vulnerable, these complications are underdiagnosed and often ineffectively treated. Patients and non-research health professionals have joined our SPOR Network to redefine interventions for the earliest diagnosis and customized treatments that will transform healthcare for all individuals with diabetes. Building on programs of excellence, our team of experts in biomedical, clinical, population and health services research, education, and knowledge translation (KT) will bridge Valleys 1 and 2 (KT gaps 1 and 2) with the following projects.

Projects

Recognizing successful models of early detection, with primary and specialty (e.g., retinopathy) care networks in BC, AB, MB, ON, QC and NS (rural, urban-rural, urban) we will launch a complications screening pilot studies to identify the best evidence-based diagnostic and data collection methods. While documenting the prevalence and incidence of diabetes in these communities, we will establish the platform for a national registry to evaluate access to and implementation of effective methods for diagnosing complications: retinopathy, nephropathy, neuropathy and cardiovascular disease. We will capture health determinants relevant to risk and progression of complications (sex, gender, socio-economic status, ethnocultural background, geography, lifestyle [diet and physical activity]) and co-morbidities (e.g., arthritis) and link this information with electronic medical records and population administrative data. By applying advanced analytics on this converged data we will develop algorithms for complex complications risk assessment necessary for the design of a unique Canadian Risk Calculator.

This smartphone communications tool will be used by patients and their healthcare providers to facilitate shared decision-making and the implementation of customized care paths. By linking clinical information about complication trajectories with new knowledge about glucose-triggered biological factors (genetics, medical imaging of affected organs, physiological study of heart and kidney function), we will identify the biomarkers of high and low risk for complications. These biomarkers will guide our first-in-human trials of therapeutics targeted at specific diabetes complications for those at high risk.

Our national patient registry and trials management platforms will provide well-phenotyped subjects for large-scale clinical and genomics studies. To achieve the best glycemic control with minimal hypoglycemia, we will evaluate the applicability and efficacy of leading-edge insulin pump therapy and a novel standards-based external artificial pancreas using a smartphone app to monitor glucose control, physical activity and other modulators. In multicentered trials, we will test new therapies discovered by our scientists for diabetic heart and kidney disease, retinopathy and neuropathy. Complementary approaches evaluated in multicentered trials will include diet and lifestyle interventions, and disease target-specific new diagnostics and therapies. Expanding on successful trials (e.g., Vigorous Physical Activity for Glycemic Control) in diabetes we will focus on the needs of populations most vulnerable to poor health outcomes (e.g., First Nations communities). We will apply easy-to-implement web-based tools with user-centred design to assess lifestyle measures (physical activity and diet) and the efficacy of personalized behaviour-modifying interventions. Informed by our Researchers-Research User’s (patients and care providers) Partnership Platform our scientists and trainees will be trained in patient-oriented research with a focus on chronic disease. We will identify where evidence about effective intervention to prevent and treat diabetes complications can drive improved health policy and cost-effective system solutions.

Impact

Our national SPOR Network will change the trajectory of diabetes complications by establishing evidence-based models of best prevention and care paths uniquely customized for patients at greatest risk, a model applicable to all chronic disease management.

Drug discovery and commercialization

A Juvenile Diabetes Research Foundation (JDRF)/NIH-funded drug screen by the Fernyhough lab in 2007-2008 identified antimuscarinic drugs as potential drivers of nerve repair in adult sensory neurons. Drs. Paul Fernyhough and Nigel Calcutt (UCSD) collaborated on a JDRF team grant starting in 2008 to perform preclinical studies to fully characterize the utility of these drugs for the treatment of diabetic neuropathy. These two labs complement each other with Fernyhough focusing on in vitro and in vivo mechanistic work and the Calcutt lab providing expertise in a variety of mouse models of neuropathy and associated clinically relevant endpoints (e.g. quantification of intraepidermal nerve fibre density in footpad). Between 2010 and 2017 this work received several sources of grant support including JDRF, CIHR and NIH. These studies generated a Journal of Clinical Investigation publication in early 2017 showing that specific or selective antagonists of muscarinic acetylcholine type 1 receptors protected from nerve damage in diabetic neuropathy, chemotherapy-induced peripheral neuropathy and a model of HIV-induced neuropathy. A new paper in Frontiers in Neuroscience is now published, one paper is accepted subject to revision at Neuropharmacology and a third paper is about to be submitted to Neuropharmacology. The submission of this muscarinic receptor-related work has been delayed to safeguard commercialization activities.

Starting in late 2010, patents were initiated via the University of Manitoba. Currently, one patent has been granted in Canada, Europe and China. Drs. Calcutt, Fernyhough and a medicinal chemist from UHN, Dr. Lakshmi Kotra, set up a small biotech start-up called WinSanTor Inc (www.winsantor.com) in late 2011 (CEO Stanley Kim). This enterprise licensed this IP from these institutes in 2012 and has instigated drug development of antimuscarinic drugs for the treatment of peripheral neuropathies. The company has successfully obtained funding support from NIH, totalling nearly US$11million, via the SBIR/STTR programs. The primary aim has been to develop topical formulations of antimuscarinic drugs, particularly pirenzepine, for therapy in neuropathic diseases. This funding has been used to support toxicity studies, pharmacokinetic work, topical formulation development, drug manufacture and a now successfully completed phase 1 trial. A small phase 2 trial in type 2 diabetic patients has been completed and showed efficacy with a topical antimuscarinic with respect to the quality of life, neuropathic endpoints and IENF levels in the skin. Larger phase 2 trials in Canada, Denmark, Germany and the USA are planned with topical pirenzepine in diabetic patients for early 2019 onwards via funding derived from a SPOR chronic disease network grant (https://diabetesaction.ca) and company resources.

At this stage the exact mechanism and/or site of action of these drugs in the context of nerve repair is unknown. It is also unknown how endogenous acetylcholine exactly modulates axonal plasticity in vivo. New studies are planned with Dr. Yves De Koninck (UofLaval) who brings unique in vivo electrophysiology and calcium imaging expertise of the DRG and distal axon to drive this work forward. While drug development continues our work aims to provide key basic science knowledge in regard to the role of endogenous acetylcholine in regulating nerve growth and identify the precise targets of antimuscarinic drug action.

Fernyhough Top publications

Eftekharpour, E. & P. Fernyhough* (2022). Oxidative stress and mitochondrial dysfunction associated with peripheral neuropathy in type 1 diabetes. Antioxidants and Redox Signaling. In press. (if 8.4).

Sequiera, G.L., Sareen, N., Aghanoori, M.R., Moudgil, M., Abu-El Rub, E., Fernyhough, P., Rockman-Greenberg, C., & S. Dhingra (2022). Establishment of iPSC based multi-systemic model and evaluation of clinical trial suitability in a patient with Leigh-like syndrome and novel mutations. Science Advances. In press. (if 14.4).

Aghanoori, M.-R., Agarwal, P., Gauvin, E., Nagalingam, R.S., Bonomo, R., Yathindranath, V., Smith, D.R., Hai, Y., Lee, S., Jolivalt, C.G., Calcutt, N.A., Jones, M.J., Czubryt, M .P., Miller, D.W., Dolinsky, V.W., Mansuy-Aubert, V. and P. Fernyhough* (2022). CEBPβ regulation of endogenous IGF-1 in adult sensory neurons can be mobilized to overcome diabetes-induced deficits in bioenergetics and axonal outgrowth. Cellular and Molecular Life Sciences. In press. (if 9.3).

Stamenkovic, A., O’Hara, K.A., Nelson, D.C., Maddaford, T.G., Edel, A.L., Maddaford, G., Dibrov, E., Aghanoori, M.R., Kirshenbaum, L., Fernyhough, P., Aliani, M., Pierce, G.N. and A. Ravandi (2021). Oxidized phosphatidylcholines trigger ferroptosis in cardiomyocytes during ischemia/reperfusion injury. American Journal of Physiology – Heart and Circulatory Physiology. 320(3): H1170-H1184. (if 4.7).

*Aghanoori, M.R., Margulets, V., Smith, D.R., Kirshenbaum, L., Gitler, D. & P. Fernyhough (2021). Sensory neurons derived from diabetic rats exhibit deficits in functional glycolysis and ATP that are ameliorated by IGF-1. Molecular Metabolism. 49, 101191. (if 7.4).

*Demaré, S., Kothari, A., Calcutt, N.A. & P. Fernyhough (2021). Metformin as a potential therapeutic for neurological disease: mobilizing AMPK to repair the nervous system. Expert Review of Neurotherapeutics. 21, 45-63.

Snow, W., Cadonic, C., Cortes-Perez, C., Adlimoghadam, A., Roy Chowdhury, S.K., Thomson, E., Anozie, A., Bernstein, M.J., Gough, K., Fernyhough, P., Suh, M., & B.C. Albensi (2020). Sex-specific effects of chronic creatine supplementation on hippocampal-mediated spatial cognition in the 3xTg mouse model of Alzheimer’s disease. Nutrients. 12, 3589. (if 5.7).

Jolivalt, C.G., Frizzi, K.E., Han, M.M., Mota, A.J., Guernsey, L., Kotra, L., Fernyhough, P. and N.A. Calcutt (2020). Topical delivery of muscarinic receptor antagonists prevents and reverses peripheral neuropathy in diabetic mice. Journal of Pharmacology and Experimental Therapeutics. 374, 44-51. (if 3.9).

Djordjevic, J., Roy Chowdhury, S., Snow, W., Perez, C., Cadonic, C., Fernyhough, P. and B.C. Albensi (2020). Early onset of sex-dependent mitochondrial deficits in the cortex of 3xTg Alzheimer’s mice. Cells. 9, 1541. (if 5.66).

Roy Chowdhury, S., Bouchard, E.D.J., Saleh, R., Nugent , Z., Peltier, C., Mejia, E., Hou, S., McFall, C., Squires, M., Hewitt, D., Davidson, L., Shen, G., Johnston, J.B., Marshal, A., Doucette, C., Hatch, G.M., Fernyhough, P., Marshall, A., Gibson, S.B., Dawe, D.E. and V. Banerji (2020). Mitochondrial respiration correlates with prognostic markers in chronic lymphocytic leukemia and is normalized by Ibrutinib treatment. Cancers. 12, 650. (if 6.6).

*Saleh, A., Sabbir, M.G., Aghanoori, M.R., Smith, D.R., Roy Chowdhury, S.K., Tessler, L., Brown, J., Gedarevich, E., Kassahun, M.Z., Frizzi, K., Calcutt, N.A. & P. Fernyhough (2020). Muscarinic toxin 7 signals via Ca2+/calmodulin-dependent protein kinase kinase  to augment mitochondrial function and prevent neurodegeneration. Molecular Neurobiology. 57, 2521-2538. (if 5.6).

Jolivalt, C.G., Marquez, A., Quach, D., Navarro Diaz, M.C., Anaya, C., Kifle, B., Muttalib, N., Sanchez, G., Guernsey, L. Hefferan, M., Smith, D.R., Fernyhough, P., Johe, K., and N.A. Calcutt (2019). Amelioration of both central and peripheral neuropathy in mouse models of type 1 and type 2 diabetes by the neurogenic molecule NSI-189. Diabetes. 68, 2143-2154 (if 7.23).

Lu, P., Kamboj, A., Hogan-Cann, A., Roy Chowdhury, S.K., Aghanoori, M.R., Fernyhough, P. and C.M. Anderson (2019). Poly(ADP-ribose) polymerase-1 inhibits mitochondrial respiration by suppressing PGC-1α activity in neurons. Neuropharmacology 160, 107755 (if 5.3).

Lu, Y., Roy Chowdhury, S.K., Lu, P., Anderson, C.M., Fernyhough, P. and H.D. Anderson (2020). Activation of cannabinoid receptors attenuates endothelin-1-induced mitochondrial dysfunction in rat ventricular myocytes. Journal of Cardiovascular Pharmacology. 75, 54-63 (if 2.6).

*Aghanoori, M.R., Smith, D.R., Levari-Shariati, S., Ajisebutu, A., Nguyen, A., Desmond, F., Calcutt, N.A., Aliani, M. and P. Fernyhough (2019). Insulin-like growth factor-1 augments mitochondrial function through AMPK to drive axonal repair and protect from sensory neuropathy in type 1 diabetes. Molecular Metabolism. 20, 149-165. (if 6.8)

2014 Senator Duhamel Award for Research Innovation

2008 Juvenile Diabetes Research Foundation, Mary Jane Kugel Award

2007 University of Manitoba Presidential Outreach Award

2006 Juvenile Diabetes Research Foundation, Mary Jane Kugel Award

1993 – 1998 Wellcome Trust Postdoctoral Fellowship Pharmacology $ 700,000
Department of Pharmacology
Queen Mary & Westfield College
University of London, United Kingdom

1991 – 1993 Merck, Sharp & Dome Pharmacology $100,000
Postdoctoral Fellowship Research Award
St. Bartholomew’s Medical College
Queen Mary & Westfield College
University of London, United Kingdom

1987 – 1989 MRC Postdoctoral Fellowship Award Cell Biology $ 90,000
MRC Cell Biophysics Unit, King’s College
London, United Kingdom

1981 – 1984 BBSRC Ph.D. Scholarship Research Award Biochemistry $ 30,000
University of Sheffield, United Kingdom

Listing of active grants

2019 – 2024
Canadian Institutes of Health Research
Total $1,090,125. (with $100k matching from WinSanTor)
Operating grant: Muscarinic receptor antagonism as a novel mechanism for sensory nerve repair.
PI: Fernyhough, P.; Co-PIs: DeKoninck, Y., U of Laval & Calcutt, N.A., UCSD
$238,025

2018-2020
St Boniface | Ben Gurion Univ. Partnership
Total $300,000.
Correcting aberrant axonal bioenergetics to drive nerve repair in neurological disease.
PI: Fernyhough, P.; Co-PI: Gitler, D.
$150,000

2018-2023
Bank of Montreal Award
Total $250,000.
Energy failure in nerve fibres: its detection and therapeutic reversal in neurological disease.
PI: Fernyhough, P.
$50,000

2020-2022
Mitacs Accelerate International
Total:  $180,000
Development of specific peptide antagonists of muscarinic receptors to repair the nervous system
PI:  Fernyhough,, P.

2019 – 2024
Canadian Institutes of Health Research
Total $1,090,125.
Operating grant: Muscarinic receptor antagonism as a novel mechanism for sensory nerve repair.
PI: Fernyhough, P.; Co-PIs: DeKoninck, Y., U of Laval & Calcutt, N.A., UCSD

2019 – 2020
St. Boniface Foundation
Total:  $100,000
Drug studies on the peripheral nervous system.
PI:  Fernyhough, P.

2018-2021
St Boniface | Ben Gurion Univ. Partnership
Total $300,000.
Correcting aberrant axonal bioenergetics to drive nerve repair in neurological disease.
PI: Fernyhough, P.; Co-PI: Gitler, D.

2018-2023
Bank of Montreal Award
Total $250,000.
Energy failure in nerve fibres: its detection and therapeutic reversal in neurological disease.
PI: Fernyhough, P.

WinSanTor Biosciences Inc.

In Fall 2018 we obtained US$2million via STTR phase 2 (follow up from Grant #4)
Title: Development of pirenzepine for CIPN
NIH Grant Number: 2 R42 CA213555-02
PI: Andrew Mizisin, WinSanTor Biosciences Inc

2017-2018
In Fall 2017 we obtained US$298,550 through the NIH STTR program to fund studies in CIPN.
Title: Development of pirenzepine for CIPN.
NIH Grant #:  1R41CA213555-01A1  PI: Andrew Mizisin, WinSanTor Biosciences Inc

2017-2018
In Spring 2017 the company was funded via NIH Commercialization Readiness Program (CRP). Funding for one year of US$997,000.
Title: Assessment of chronic toxicity to support the use of topical pirenzepine for treating diabetic neuropathy. NIH Grant #: 2SB1DK104512-04 PI: Stanley Kim, CEO WinSanTor Biosciences Inc

2014-2017
In Fall 2014 we obtained US$2.25million through NIH SBIR (Fast Track; via NIDDK) program to fund further drug development. Rated highest application in competition.
Title: Pre-Clinical Development of Topical Pirenzepine for Treating Diabetic Neuropathy.
NIH Grant #: 1R44DK104512-01 PI: Stanley KIM, CEO WinSanTor Biosciences Inc

2012-2015
In Fall 2012 we obtained US$7.3million through the NIH Type 1 Diabetes – Rapid Access to Intervention Development (T1D-RAID; via NIDDK) program that will oversee the development of the drug.
Title: Topical pirenzepine to treat diabetic neuropathy.
PI: Stanley KIM, CEO WinSanTor Biosciences Inc

NIH award – SBIR program – NIDDK – 2R44DK104512-05
Regeneration of Epidermal Nerves in Human Diabetic Neuropathy
PI: Kim, S. CEO of WinSanTor Inc.
Period Of Performance:
Budget Period: 05/01/2019 – 04/30/2020
Project Period: 09/30/2014 – 04/30/2022

SUMMARY TOTALS FOR YEARS 5-7

Yr 5 US$1,000,000
Yr 6 US$995,582
Yr 7 US$985,495

NIH award – SBIR program – Cancer – 2SB1CA213555-04
Submission of Investigational New Drug application to the Federal Drug Administration to support clinical development of topical pirenzepine for CIPN
PI: Mizisin, A., WinSanTor Biosciences Inc.
7/15/2020-07/14/2021
US$250,000

NIH award – SBIR program – Neurological Disorders & Strokes – Combination – 1R41NS120354-01
Development of a topical fixed-dose combination drug for peripheral neuropathic pain
Hansen, A., WinSanTor Biosciences Inc.
9/30/2020-08/30/2022
US$699,491

Current Research group

Darrell Smith – Senior Scientist

Farhana Naznin – Post Doctoral Fellow

TM Zaved Waise – Post Doctoral Fellow

Shayan Amiri –  Ph.D. Graduate Student

Sanjana Chauhan – Ph.D. Graduate Student

Pranav Mishra Ph.D. Graduate Student

Doris Goubran –  Undergraduate Student

Amila Hoang – Undergraduate student

Annie Jiang – Undergraduate Student

Marvellous Oyeyode – Undergraduate Student

Serena Phillips –  Undergraduate Student

Lauren Verhaeghe – Undergraduate Student

Jeffrey Wilson – Undergraduate Student 

Lori Tessler –  Technician

Debbie Fowler – Glasswash Technician

Kelly Jorundson – Administrative Manager