IHN Thesis Mentors 2017

IHN Masters of Science
Thesis Mentors 2017

INSTITUTE OF HUMAN NUTRITION, COLUMBIA UNIVERSITY MEDICAL CENTER

Basic Science

Armin Alaedini, PhD

Assistant Professor, Department of Medicine
Email: [email protected]
Phone: 212 851-4582
Departmental website
Alaedini Lab website

Bio

Dr. Alaedini received his BS from Ohio State University and his PhD in biochemistry at the
University of Cincinnati. He is currently an assistant professor in the Department of Medicine
and at the Institute of Human Nutrition. He is also the director of laboratory research at the
Celiac Disease Center.

Research Objectives

Armin Alaedini's laboratory utilizes a multidisciplinary approach that includes proteomics,
immunology, biochemistry, and molecular biology to study host-microbe interactions and the
role of microbial and dietary antigens in immune-mediated mechanisms affecting the
gastrointestinal (GI) and nervous systems. Our research is focused on the following areas:

Research Area 1 – Inflammatory response to dietary and microbial molecules in the context of
gasatrointestinal and neuropsychiatric disease—investigating the gut-immune-brain
connection.

Human intestinal mucosal surfaces are colonized by large communities of microorganisms and
are in constant contact with an abundance of highly immunogenic dietary and microbial
components. Proper regulation of the interaction between the host and the contents of the
gastrointestinal (GI) tract is of utmost importance in avoiding aberrant immune responses and
requires several different mechanisms. Failure of one or more of these regulatory mechanisms
can adversely affect human health, not only through GI disorders, but also via systemic
manifestations that may influence cognition and behavior. A primary goal of our group is
investigation of the role of mucosal inflammation and intestinal barrier function in the context

MS Thesis Mentors Institute of Human Nutrition 2

of GI and neuropsychiatric symptoms. Disease focus areas in our lab include celiac disease, non-
celiac wheat/gluten sensitivity, irritable bowel syndrome, autism spectrum disorders, and
myalgic encephalomyelitis/chronic fatigue syndrome.

Research Area 2 – Mechanisms and biomarkers of post-infection persistence of inflammation
and symptoms.

There is evidence that persistence of symptoms following antibiotic treatment of certain
infections may be immune-mediated. A critical barrier to a better understanding of the
mechanisms involved has been the lack of biomarkers to characterize disease phenotypes and
analyze treatment outcome. Our laboratory is conducting studies to understand the connection
between the bacterial strain genotype in specific infections, host immune response, and the
persistence of inflammation and symptoms following infection. We are also working towards
establishing biomarkers to predict the risk of developing post-infection symptoms. Our work in
this context has been primarily focused on infection with Borrelia burgdorferi, the causative
agent of Lyme disease, which is the most common vector-borne infection in the United States
and Europe.

Notes for Students

• Experience: Bench research experience (especially pipetting and preparation of solutions)
would be helpful to the student’s success.

• Worksite dynamics: The student will work relatively independently but will be closely
supervised by the PI. Projects within larger studies will involve interaction with and
additional supervision by a post-doctoral fellow or research associate.

• Research type: basic science/translational (cell culture/benchtop)
• Required trainings: laboratory safety/chemical hygiene and blood-borne

pathogen/biosafety training. These trainings are offered online through Rascal.
• Background reading: basic immunology, celiac disease/gluten sensitivity; Lyme disease;

chronic fatigue syndrome; autism
• Number of students: 2 students
• Location: Columbia University Medical Center; ICRC 901B
• Additional information: provided upon request

MS Thesis Mentors Institute of Human Nutrition 3

Basic Science

Mildred Embree, DMD, PhD

Assistant Professor, College of Dental Medicine, Columbia University
Email: [email protected]
Phone: 212-305-4475
Department website
Lab website

Bio

Dr. Mildred Embree is a dentist scientist specializing in temporomandibular joint and
musculoskeletal biology and diseases, stem cells and regenerative medicine.

Research Objectives

Research at the Laboratory of TMJ Biology and Regenerative Medicine has identified TMJ stem
cells or termed fibrocartilage stem cells that spontaneously regenerate cartilage and bone
when transplanted in vivo. Our efforts are dedicated to deciphering the key players comprising
the TMJ stem cell niche and regulatory pathways that are critical for TMJ stem cell fate
specification during development. Lessons learned from the fundamental biological concepts
discovered in our lab are used to dissect the molecular underpinnings gone awry during TMJ
disease pathogenesis. Collectively, we use our basic and pathological scientific findings to serve
as the foundation and building blocks essential for developing regenerative medicinal strategies
to treat musculoskeletal disease, such as temporomandibular disorders and osteoarthritis.

Notes for Students

• Experience: Given this independent nature, preference is given to those with prior
benchtop experience.

• Worksite dynamics: Students will work independently, but have access to staff associate
scientists and post docs for further guidance.

• Research type: basic science (animal subjects)

MS Thesis Mentors Institute of Human Nutrition 4

• Required trainings: Students may have to take animal training in order to access and handle
mice.

• Background reading: Provided upon request
• Number of students: 1-2 students
• Location: provided upon request
• Additional information: provided upon request

MS Thesis Mentors Institute of Human Nutrition 5

Basic Science

John Glendinning, PhD

Associate Professor of Nutritional Medicine
Department of Medicine, Columbia University Medical Center
New York Obesity Nutrition Research Center
Email : [email protected]
Phone : 212-851-5578
Department website

Bio

Dr. Glendinning is the Ann Whiney Olin Professor of Biology at Barnard College. He received his
PhD from the University of Florida in Zoology, and conducted postdoctoral training at Florida
State University and the University of Arizona. He teaches course in physiology, statistics and
research design.

Research Objectives

His research seeks to understand the physiological underpinnings one of life's great pleasures:
eating. He is interested in how the brain uses input from sensory systems in the mouth and gut
to determine (a) the chemical composition of foods, (b) whether we like or dislike a particular
food, and (c) which metabolic responses should be activated (e.g., insulin release) so as to
facilitate post-absorptive processing of the food. He also examines how pre- and post-natal
experience with foods can make them more palatable. Some of his most recent projects have
addressed the following questions:

1. How does taste input interact with other feeding-related inputs (e.g., sensory inputs from
the gut) to stimulate or inhibit feeding?

2. Why does fetal alcohol exposure make alcohol more acceptable to adolescents?
3. Can mammals distinguish between sugars and artificial sweeteners? If so, how?
4. How does the mere taste of glucose stimulate insulin release from beta cells in the

pancreas?
5. Why do cancer chemotherapy treatments make foods unpalatable?

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Notes for Students

• Experience: The candidate must be willing to work with the mice and have some bench
research experience.

• Worksite dynamics: The student will collaborate with the mentor and other students in the
laboratory.

• Research type: basic science (rodents - using a combination of behavioral,
electrophysiological, and molecular approaches)

• Required trainings: Student will need to obtain IACUC certification for working with mice.
• Background reading: Recent Publications (Barnard and Columbia students in Italics):

[1] Glendinning JI, Tang J, Allende APM, Bryant BP, Youngentob L, Youngentob SL (2017)
Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminal
chemosensory neurons to ethanol and its flavor components. Journal of Neurophysiology
118: 1198–1209
[2] Glendinning JI, Frim YG, Hochman A, Basile AJ, Lubitz G, Sclafani A (2017) Glucose elicits
cephalic-phase insulin release in mice by activating K(ATP) channels in taste cells. American
Journal of Physiology 312: R597–R610
[3] Wang T, Glendinning J, Grushka M, Hummel T, Mansfield K (2017) Drug-induced taste
disorders in clinical practice and preclinical safety evaluation. Toxicological Sciences 156(2):
315–324
[4] Bachmanov AA, Bosak NP, Glendinning JI, Inue M, Li X, Manita S, McCaughey SA, Murata
Y, Reed DR, Tordoff MG, Beauchamp, GK (2016) Genetics of amino acid taste and appetite.
Advances in Nutrition 7 (Suppl): 806S–822S
[5] Glendinning JI (2016) Do low-calorie sweeteners increase weight gain in rodents?
Physiology & Behavior 164: 509–513.
[6] Glendinning JI, Stano S, Holter M, Azenkot T, Goldman O, Margolskee RF, Vasselli J,
Sclafani A (2015) Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-
independent taste transduction pathway in mice. American Journal of Physiology 309:
R552-R560
• Number of students: 1 students
• Location: 07 Altschul Hall, Barnard College, 116th & Broadway
• Additional information: provided upon request

MS Thesis Mentors Institute of Human Nutrition 7

Basic Science

Michael Goldberg, MD

David Mahoney Professor of Brain and Behavior
Director, Mahoney Center
Departments of Neuroscience & Psychiatry, Columbia University
Medical Center
Email : [email protected]
Phone : 646-774-7389
Department website
Lab website

Bio

N/A

Research Objectives

We study the psychophysics and physiology of cognitive processes in the monkey, using single
unit recording, iontophoresis, and careful behavioral measurements. The thrust of the lab has
been understanding the physiology of visual attention - how the brain selects important objects
in the visual field for further processing - and the generation of spatially accurate behavior
despite a constantly moving eye. Current projects include studying the role of somatosensory
cortex in the eye-position modulation of visual responses in parietal cortex; studying a newly
discovered untuned cholinergic modulatory signal in the monkey parietal cortex that predicts
how well the monkey will perform on the current trial of a difficult task, correlates inversely
with the monkey's recent history of success or failure, and correlates positively with the
neuron's response to a visual transient; studying the involuntarily establish of spatial memory
memory in the lateral intraparietal area and the parahippocampal gyrus, studying the fine
structure of perisaccadic remapping of visual receptive fields, and studying the role of the
cerebellum in visualmotor associations. Recent discoveries in the laboratory include the
demonstration of a predictive relationship of parietal activity to both saccadic reaction time and
visual attention; the demonstration that the lateral parietal area acts as a linear summing
junction for at least three independent signals: a saccadic signal, and undifferentiated visual
signal, and a cognitive signal, and the proprioceptive representation of eye position in monkey

MS Thesis Mentors Institute of Human Nutrition 8

area 3a of primary somatosensory cortex, and the time course of eye-position modulation of
visual responses in the parietal cortex.

Notes for Students

• Experience: none specifically listed
• Worksite dynamics: none listed
• Research type: basic science (animal subjects)
• Required trainings: TBD
• Background reading: provided upon request
• Number of students: TBD
• Location: Our lab is located at the NYS Psychiatric Institute, in the brown brick building

known as the Kolb Annex: (40 Haven Av, New York, NY, 10032)
• Additional information: provided upon request

MS Thesis Mentors Institute of Human Nutrition 9

Basic Science

Rebecca Haeusler, PhD

Assistant Professor of Pathology & Cell Biology
Department of Pathology & Cell Biology,
Columbia University Medical Center
Email : [email protected]
Phone : 212-851-4899
Department website
Lab website

Bio

Dr. Rebecca Haeusler is an assistant professor in the Department of Pathology and Cell Biology.
Her research focuses on understanding the development of pro-atherogenic metabolic
abnormalities in the natural history of diabetes and the metabolic syndrome.

Research Objectives

People with diabetes, obesity, and insulin resistance display multiple metabolic abnormalities.
These include high blood glucose, high triglycerides, and multiple alterations in cholesterol
metabolism. We are investigating these metabolic pathways.

Notes for Students

• Experience: Bench research experience is necessary. Experience in molecular biology, cell
culture or animal handling is necessary.

• Worksite dynamics: Students will work in collaboration with mentor and with other lab
members.

• Research type: basic science (measuring hormones and metabolites, preparing RNA and
DNA, performing PCR) There is potential for mouse handling, depending on experience.

• Required trainings: provided upon request
• Background reading: provided upon request
• Number of students: 1 student
• Location: Russ Berrie Pavilion
• Additional information: provided upon request

MS Thesis Mentors Institute of Human Nutrition 10

Basic Science

Yiping Han, PhD

Professor of Microbial Sciences,
Department of Dental Medicine, Microbiology & Immunology
Columbia University
Email : [email protected]
Phone : 212-342-1414
Department website
Lab website

Bio

Dr. Hang is a Professor of Microbial Sciences in Dental Medicine and Microbiology &
Immunology at CUMC. Her research focuses on Host-pathogen interactions, human
microbiome, oral-systemic connections.

Research Objectives

Investigating the role of oral bacteria in extra-oral infection and inflammation. Increasing
evidence suggests that microbial communities specific to particular regions of the body are not
isolated from each other but rather are mobile and interchangeable. For example, oral bacteria
are not limited to the confines of the mouth and are frequently detected at extra-oral sites
associated with infections and inflammation. We investigate the impact of the oral microbiome
and oral health on pregnancy complications and gastrointestinal (GI) disorders.

Investigating the mechanisms of Fusobacterium nucleatum pathogenesis in pregnancy
complications and colorectal cancer. F. nucleatum is a gram-negative anaerobic oral commensal
prevalent in pregnancy complications including preterm birth, stillbirth, and neonatal sepsis. It
has also been associated with GI disorders, including inflammatory bowel disease, colorectal
cancer, and appendicitis. We have identified a unique adhesin, FadA, from F. nucleatum that
plays an essential virulent role. FadA is thus a potential diagnostic and therapeutic target for
disease detection and prevention. Our studies on FadA include continued analysis of its
structure, function, regulation, as well as its clinical relevance in disease diagnoses, treatment,
and prevention.

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Developing genetic tools for mutant construction in bacteria. Studies of microbes are often
hindered by the lack of genetic tools. My lab developed the technique to deliver DNA into
bacteria by ultrasound, and we constructed the first double-crossover allelic exchange mutant
in F. nucleatum. Developing bacterial genetic tools continues to be a focus in our lab.

Notes for Students

• Experience: none specifically listed
• Worksite dynamics: none specifically listed
• Reserach type: basic science
• Required trainings: none specifically listed
• Background reading: provided upon request
• Number of students: TBD
• Location: Hammer Health & Science, 15-1514, 15-1514A, and 15-1516, CUMC
• Additional information: provided upon request

MS Thesis Mentors Institute of Human Nutrition 12

Basic Science

Kara Margolis, MD

Associate Professor of Pediatrics
Department of Gastroentrology, Columbia University Medical Center
Email : [email protected]
Phone : 212-305-5903
Department website

Bio

N/A

Research Objectives

Our laboratory studies the role of neurotransmitters (mostly serotonin) in enteric nervous
system development, motility disorders, inflammatory bowel disease and autism spectrum
disorders. We have most recently between examining serotonin as a brain-gut link in autism
and antenatal antidepressant exposure.

Notes for Students

• Experience: The ideal candidate will work well with a team, be comfortable handling mice
and have enough basic background in lab techniques that they know that they enjoy basic
science.

• Worksite dynamics: The student will work collaboratively with me and my technicians (both
former nutrition Master's students).

• Research type: basic science (animal studies)
• Required trainings: If they are able they should undergo mouse handling training and

approval but this is not a necessity.
• Background reading:

[1] Margolis KG**, Li ZS, Stevanovic K, Saurman V, Israelyan N, Blakely R, Veenstra-
Vanderweele J and Gershon MD. Serotonin Transporter Variant Drives Preventable
Gastrointestinal Abnormalities in Development and Function. Accepted at the Journal of
Clinical Investigation. J Clin Invest. 2016 Jun 1;126(6):2221-35. doi: 10.1172/JCI84877. Epub
2016 Apr 25.

MS Thesis Mentors Institute of Human Nutrition 13

[2] Marler S, Ferguson BJ, Lee EB, Peters B, Williams KC, McDonnell E, Macklin EA, Levitt P,
Gillespie CH, Anderson GM, Margolis KG, Beversdorf DQ, Veenstra-VanderWeele J. Brief
Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum
Disorder. J Autism Dev Disord. 2015 Nov 2. [Epub ahead of print].
[3] Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation
in mouse intestine. Margolis KG, Stevanovic K, Li Z, Yang QM, Oravecz T, Zambrowicz B,
Jhaver KG, Diacou A, Gershon MD. Gut. 2014 Jun;63(6):928-37. doi: 10.1136/gutjnl-2013-
304901. Epub 2013 Jun 7.
[4] Enteric neuronal density contributes to the severity of intestinal inflammation. Margolis
KG, Stevanovic K, Karamooz N, Li ZS, Ahuja A, D'Autréaux F, Saurman V, Chalazonitis A,
Gershon MD. Gastroenterology. 2011 Aug;141(2):588-98, 598.e1-2. doi:
10.1053/j.gastro.2011.04.047. Epub 2011 Apr 28.
[5] Neuropeptides and inflammatory bowel disease. Margolis KG, Gershon MD. Curr Opin
Gastroenterol. 2009 Nov;25(6):503-11. doi: 10.1097/MOG.0b013e328331b69e. Review.
[6] Serotonin has a critical role in the pathogenesis of experimental colitis. Margolis KG,
Pothoulakis C. Gastroenterology. 2009 Nov;137(5):1562-6. doi:
10.1053/j.gastro.2009.09.027. Epub 2009 Sep 27
• Number of students: 2 students

• Location: black building 1119

• Additional information: provided upon request

MS Thesis Mentors Institute of Human Nutrition 14

Basic Science

Cathy Mendelsohn, PhD

Associate Professor of Nutritional Medicine
Department of Medicine, Columbia University Medical Center
New York Obesity Nutrition Research Center
Email : [email protected]
Phone : 212-851-5578
Department website

Bio

Dr. Mendelsohn is a professor of urology, pathology & cell biology, and genetics &
development. She completed her PhD at Columbia University in 1989. She did her postdoctoral
work at IGBMC in 1994, and at Columbia University in 1997. Her lab investigates urothelial
progenitors—which are important for formation, homeostasis, and regeneration of the
urothelium—and identification of urothelial cell types that give rise to cancer.

Research Objectives

Identification of progenitors important for Urothelial Development and Regeneration, and cells
of origin for bladder cancer.
The urothelium is a specialized epithelium extending from the renal pelvis to the bladder that is
critical for preventing exchange of water and toxic substances between the urinary tract and
the blood. The urothelium is also thought to be a source of cells that generate different types of
bladder cancers, including carcinoma in situ, papillary carcinoma, invasive cancers and
squamous cell carcinoma.
Projects:
[1] Using mouse models in fate mapping studies to identify progenitors that give rise to the
urothelium during development and regeneration, coupled with RNAseq to identify signaling
pathways that are normally important for these events.
[2] We showed recently that vitamin A (retinoic acid) is required in distinct progenitor
populations for urothelial development and regeneration, respectively. To understand how
retinoids work, we are sorting different urothelial cells from RA-mutants and controls then
comparing their gene expression profiles using RNAseq.

MS Thesis Mentors Institute of Human Nutrition 15

[3] We are using mouse models of carcinogenesis coupled with fate mapping to identify cells of
origin that give rise to papillary carcinoma, carcinoma in situ, squamous cell carcinoma and
invasive bladder cancers.

Developmental Studies to understand the etiology of urinary tract birth defects.
We are interested in the causes of hydronephrosis, a birth defect that in humans and mouse
models is associated with severe kidney damage. Hydronephrosis can be caused by abnormally
positioned distal ureters, which join the bladder outside the proper insertion site, or can be
linked to bladder/urethral abnormalities such as urethral valves, a common defect found in
newborn boys that results in urethral obstruction, bilateral hydronephrosis and renal damage.
We are currently studying the cause of distal ureter abnormalities using Caspase knockout mice
in which apoptosis, which is critical for proper insertion of ureter in the bladder is impaired.

Notes for Students

• Experience: should be okay with handling mice
• Worksite Dynamics: The students will work in collaboration within the lab.
• Research Type: basic science (animals)
• Required Trainings: TBD
• Background reading: TBD
• Number of Students: 1-2 students
• Lab location: 311 Irving Cancer Research Center
• Additional Information: provided upon request

MS Thesis Mentors Institute of Human Nutrition 16

Basic Science

John Morrow, MD

Assistant Professor of Medicine, CUMC
Email : [email protected]
Phone : email preferred
Department website

Bio

Dr. Morrow is an Assistant Professor of Medicine at Columbia University Medical Center where
he specializes in Cardiac Electrophysiology and Cardiology. His research focuses on ion channel
regulation and translational research in cardiac electrophysiology.

Research Objectives

The goal of my research is to determine the molecular mechanisms that connect metabolic
diseases (obesity and diabetes) to abnormal cardiac electrophysiology, arrhythmias, and heart
failure. This is an extension and expansion of my prior work in the areas of ion channel function
and the cellular biology of lipid metabolism. I apply molecular biology, cellular physiology, and
in vivo heart rhythm techniques to improve our understanding of cardiac lipid overload. Despite
the increasing prevalence of obesity and diabetes, little is known about the contribution of
metabolic abnormalities to the pathophysiology of heart failure, arrhythmias, and sudden
cardiac death. I have extensive experience with small animal survival surgery, cardiomyocyte
isolation, patch clamp, immunohistochemistry, cell culture, and standard molecular biology
techniques. I am also dedicated to educating and training the next generation of cardiovascular
researchers, both students and post-docs. Four IHN students have completed a thesis in my lab,
and three of them have gone on to medical school. One has since completed medical school
and is now an internal medicine resident at Beth Israel Deaconess Hospital, a Harvard program.
I have also served on the thesis committee of PhD students. As a physician-scientist, I devote
75% of my time to laboratory research. My work as a clinical cardiac electrophysiologist informs
my translational research program. My ultimate goal is to develop novel therapeutics to
prevent the ion channel remodeling and arrhythmias caused by cardiomyocyte lipid overload.

MS Thesis Mentors Institute of Human Nutrition 17

Notes for Students

• Experience: Recommended that applicants have prior experience with rodents and/or cell
culture.

• Worksite dynamics: The students will work in collaboration with post-doc Leroy Joseph,
lcj2117

• Research type: basic science (animals, cell culture)
• Required trainings: provided upon request
• Background reading: Diet-induced obesity causes long QT and reduces transcription of

voltage-gated potassium channels. Journal of Molecular and Cellular Cardiology 59 (2013)
151–158
• Number of students: 1 students
• Lab location: Black Building, CUMC
• Additional information: provided upon request

MS Thesis Mentors Institute of Human Nutrition 18

Basic Science

David Paik, MD

Assistant Professor of Ophthalmic Science, Ophthalmology, Columbia
University Medical Center
Email: [email protected]
Phone: 212-342-5455
Department website

Bio

Dr. Paik graduated from Dartmouth College and received his MD degree from Temple
University School of Medicine. He trained in general surgery and surgical critical care at St.
Luke’s/Roosevelt Hospital in NYC. Since then, he has transitioned into biomedical research and
now runs an NIH-funded research program in the department of Ophthalmology. Believe it or
not, he’s been at P&S for almost 20 years!

Research Objectives

We are trying to change the mechanical properties of the cornea [and other tissues] using
chemical cross-linking compounds that are in commercial use as cosmetic preservatives. We
need help carrying out live rabbit studies in collaboration with Dr. Taka Nagasaki in the
Department of Ophthalmology here at the Columbia University Medical Center. Mechanical
testing is being carried out in the Department of Mechanical Engineering at the Columbia
University main campus. This will be an interesting project for the student to become involved
with. We image the cornea in real-time using an intra-vital confocal microscopy system while
treating the cornea with cross-linking agent. We are trying to determine if there is a best way
to induce the mechanical property change in the extracellular matrix without significantly
damaging the cells. Current clinical practice involves the use of ultraviolet light and requires
removal of the corneal epithelium which is painful and can increase one’s risk of infection. It is
being used effectively throughout the world, however, including the U.S., where it recently
gained FDA approval.

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Notes for Students

• Experience: N/A
• Worksite dynamics: The students will assist Mariya Zyablitskaya, M.D. and Anna Takaoka,

Ph.D. in carrying out the live animal studies in collaboration with Prof. Taka Nagasaki.
• Research type: basic science (animal research, pre-clinical studies, translational research)
• Required trainings: Laboratory safety on-line coursework and animal rabbit training (on-line

and wet lab). These are available on Rascal.
• Background reading: TBD
• Number of students: 1-2 students
• Location: Edward S. Harkness Eye Institute, 160 Fort Washington Ave (at 165th St) Research

Annex Rooms 715 and 716, New York, NY 10032
• Additional information: Co-mentor: Takayuki Nagasaki, Assistant Professor in

Ophthalmology ([email protected], 212-305-4654)

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Basic Science

Matthias Quick, PhD

Assistant Professor of Clinical Neurobiology
Department of Psychiatry & Center for Molecular Recognition, CUMC
Email : [email protected]
Phone : 212-854-4749
Department website

Bio

Dr. Quick is an Assistant Professor of Neurobiology in the Department of Psychiatry and in the
Center for Molecular Recognition at the Columbia University Medical Center, and Research
Scientist V in the New York State Psychiatric Institute Division of Molecular Therapeutics.

Research Objectives

Secondary active transport proteins play a central role in fundamental cellular processes such
as the regulation of serum ion concentrations in the kidney, the selective transport of nutrients,
vitamins, and ions from foodstuff in the gut, and neurotransmission. Their malfunction often
leads to clinical manifestations such as disorders of blood pressure, malabsorption syndromes,
and psychiatric disorders. As a consequence, transport proteins have gained a central role in
the treatment of the aforementioned diseases and many of the most widely prescribed drugs
(e.g., hydrochlorothiazide, omeprazole, sertraline, and fluoxetine) target transport proteins
where they act as diuretics, antihypertensives, and antidepressants. Despite our increasing
knowledge of the structures of membrane transport proteins, understanding the mechanism by
which the energy of the transmembrane electrochemical ion gradients is translated into the
coupled transport of other molecules across the membrane is still a major challenge. To gain
insight into the molecular events that govern sodium-coupled transport the Quick lab focuses
on the allosteric interaction of two substrate binding sites in the human sodium/multivitamin
transporter (hSMVT) and how this interaction is required for coupled transport. The results of
this project are expected to lead to a novel paradigm for the mechanism of ion-gradient
coupled membrane transport, a central feature in the biology of all living systems.

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Notes for Students

• Experience: basic molecular biology; general knowledge about cell culture; basic protein
analytical knowledge (SDS-PAGE; Western blot); desired: two-electrode voltage-clamp

• Worksite dynamics: relatively independently
• Research type: basic science (benchtop work)
• Required Trainings: CUMC's lab safety training and hazardous waste management training;

radioactivity training.
• Background reading: provided upon request
• Number of students: 1 students
• Location: Kolb Research Annex, 3rd floor; 40 Haven Ave, New York, NY 10032
• Additional Information: provided upon request

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Basic Science

Alex J. Rai, PhD

Assistant Professor of Pathology & Cell biology, and Director of
Special Chemistry Laboratory, Department of Pathology, CUMC
Email: [email protected]
Phone: 212-305-4475
Department website

Bio

Dr. Rai is an Associate Professor of Pathology here at Columbia University Medical Center, and
is the director of Special Chemistry Laboratory, where they perform laboratory testing in an era
of personalized medicine through the use of multiplexed gene expression and
pharmacogenetics analysis.

Research Objectives

The goal of this project will be to use molecular (DNA & RNA) and/or proteomic (protein-based)
approaches to identify biomarkers residing within exosomes derived from clinical fluids (such as
serum). One aspect will entail optimizing methods to purify exosomes from serum samples. We
will use recently identified biomarkers (from our lab) to better understand signaling pathways
associated with diseases such as cancer and to delineate communication signals within and
between cells (this will be done using web based databases and bioinformatics programs in our
lab). These biomarkers can potentially serve as drug targets and can also help delineate the
underpinnings of the disease process. Ultimately, such markers can be used to design clinical
tests that are useful for patient management (a final part of the project will be to help design
and validate such a clinical assay).

Notes for Students

• Experience: Limited bench research experience is desirable, but we will train as needed in
all the required methods/approaches.

MS Thesis Mentors Institute of Human Nutrition 23

• Worksite dynamics: Students will work with an experienced technologist and will meet
briefly with mentor at least 2-3x/week.

• Research type: basic science (bench work)
• Required trainings: TBD
• Background reading: TBD
• Number of students: 2 students
• Location: provided upon request
• Additional information: provided upon request

MS Thesis Mentors Institute of Human Nutrition 24

Basic Science

Meenakshi Rao, MD, PhD

Assistant Professor of Pediatrics
Department of Gastroentrology, Hepatology and Nutrition, Columbia
University Medical Center
Email : [email protected]
Phone : 212-342-3647
Department website

Bio

Dr. Rao obtained her MD and Ph.D. (Neuroscience) at Johns Hopkins School of Medicine and
then completed residency training in Pediatrics and subspecialty training in Pediatric
Gastroenterology, Hepatology and Nutrition at Boston Children’s Hospital (Harvard Medical
School). She joined the Columbia faculty in 2013 and is a physician-scientist, spending one day a
week caring for children with GI disorders and the rest of her time directing a research lab
focused on understanding how the enteric nervous system (ENS) regulates digestion and
metabolic homeostasis.

Research Objectives

The GI tract is unique among all other organs because it has its own intrinsic nervous system
that can function largely independently to regulate a variety of digestive and metabolic
functions. My lab uses mouse genetic models and both in vivo and in vitro assays to investigate
how information about nutrients and microbes is detected and used by the ENS to regulate GI
motility, appetite, epithelial repair and immune responses. Our work is directly relevant to
digestive disorders and obesity.

Notes for Students

• Experience: Laboratory experience preferred but not required.
• Worksite dynamics: small lab that is an interactive, collaborative team environment
• Research type: basic science - neuroscience, gastrointestinal biology
• Required trainings: Lab Safety, ICM animal training

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• Background reading: Rao M, Gershon MD. The bowel and beyond: the enteric nervous
system in neurological disorders. Nature Reviews Gastroenterology and Hepatology. PMID:
27435372.

• Number of students: 1-2 students
• Location: P&S 9-401
• Additional information: My lab has been an excellent training environment for IHN

students interested in gaining basic science experience relevant to neuroscience and/or GI
biology. Comfort working with mice is helpful but there are bioinformatics or cell culture
projects available for select students who have prior experience in one of these areas.

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Basic Science

Emily Tsai, MD

Assistant Professor of Medicine
Department of Cardiology, Columbia University Medical Center
Email : [email protected]
Phone : 212-305-3409
Department website

Bio

Dr. Tsai is an Assistant Professor of Medicine at Columbia University Medical Center in the
Department of Medicine, Division of Cardiology. A physician-scientist, Dr. Tsai studies molecular
signaling of heart failure in animal models as well as in patients. As an advanced heart failure
and transplant cardiologist, she also takes care of patients in the Center for Advanced Cardiac
Care at New York Presbyterian Hospital.

Research Objectives

The Tsai laboratory studies molecular mechanisms of abnormal cardiac signaling with the goal
of discovering novel therapies for heart failure. Our team focuses on two interconnected areas
of research: 1) dysregulation of cyclic guanosine monophosphate (cGMP) signaling in treated
versus untreated heart failure; and 2) molecular mechanisms underlying right ventricular
dysfunction. Project 1: Dysregulation of cGMP in treated versus untreated heart failure.
Despite current evidence-based therapies, heart failure (HF) remains a fatal diagnosis with a
markedly high absolute mortality rate. Innovative and improved HF therapies are urgently
needed for these patients who already receive guideline directed medical therapy (GDMT).
Cyclic guanosine monophosphate (cGMP), a ubiquitous second messenger in the cardiovascular
system, is known to mediate cardioprotective signaling. Novel pharmacotherapies that
enhance cGMP signaling have shown some therapeutic promise in HF, yet different strategies
have yielded variable results in recent clinical trials. Such inconsistencies highlight our limited
understanding of abnormal cGMP signaling in the HF patient taking β-adrenergic blockers,
angiotensin converting enzyme inhibitors, and mineralocorticoid receptor antagonists--- the

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cornerstones of GDMT. The fundamental discrepancy lies in the fact that clinical trials enroll HF
patients on concurrent GDMT, whereas preclinical studies to date use untreated HF animal
models to develop and test novel HF drugs. The molecular signaling of GDMT-treated HF differs
from that of untreated HF. This project seeks to determine how GDMT alters cGMP signaling in
the chronically failing heart, thereby identifying novel strategies to effectively exploit the
therapeutic potential of cGMP signaling and other cardioprotective pathways. Project 2:
Molecular pathophysiology of right ventricular dysfunction. Right ventricular dysfunction (RVD)
independently confers increased morbidity and mortality amongst heart failure patients,
irrespective of their left ventricular ejection fraction. Despite the high prevalence of RVD, none
of the current guideline-directed medical therapies for chronic heart failure prevent or reverse
RVD. In fact, medical treatment of RV failure is entirely empiric and emphasizes volume
management and inotropic support, neither of which improves long-term survival. Already
proven to be functionally beneficial in advanced pulmonary arterial hypertension patients,
novel cGMP enhancing drugs also hold promise in treatment of chronic heart failure. cGMP is a
ubiquitous second messenger in the cardiovascular system, mediating physiologic actions in
various cell types, including cardiac myocytes, cardiac fibroblasts, vascular smooth muscle cells,
endothelial cells, renal glomerular pericytes, and renal ductal principal cells. Different cGMP
enhancing drugs, however, target different signaling molecules and have had variable outcomes
in heart failure clinical trials; their direct myocardial effects, particularly in the failing right
ventricle, are incompletely understood. Using both animal models of heart failure and
myocardial tissue from end-stage heart failure patients, we have discovered novel mechanisms
by which the nitric oxide (NO) biosensor, soluble guanylyl cyclase (sGC), is dysregulated in the
pathologically remodeled heart and further identified interventricular differences in NO-sGC-
cGMP signaling in the heart with biventricular failure. As we gain more insight into these
interventricular signaling differences, we expect to devise strategies for modifying cGMP
signaling that will improve biventricular function of the failing heart. Our studies also aim to
identify other molecular mechanisms unique to right ventricular dysfunction. We are currently
collaborating with investigators at UCLA using weighted gene co-epxression network analysis to
identify unique genetic drivers of RV dysfunction and genetic protectors against RV failure. This
project aims to validate these candidate genes in an animal models of RV dysfunction and in a
larger cohort of HF patient samples, to select the most promising gene candidate for targeted
RVD-specific intervention, and test the therapeutic potential of the RVD-specific intervention.
The ultimate goal of the Tsai lab is to discover novel approaches for the treatment of chronic
heart failure, with an emphasis on preventing and reversing right ventricular failure.

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Notes for Students

• Experience: Bench research experience is required. Animal handling experience is preferred
but not required. Candidates should have experience in some of the following
techniques/methods: RNA extraction and quantitation, quantitative real-time RT-PCR, PCR
primer design, protein extraction and quantitation, western immunoblot and analysis,
immunohistochemistry and/or immunocytochemistry, ELISA, cell culture

• Worksite dynamics: The student(s) will work in collaboration. They will be mentored by the
PI, Dr. Emily Tsai. Post-doctoral research scientist, Dr. Yanan Liu, PhD, will also assist in daily
supervision of the student(s).

• Research type: basic science (human subjects, animal subjects, translational research)
• Required trainings: Students should complete the below RASCAL training courses: TC0094 -

RCR TC0900 - Introduction to ICM TC0800 - Mouse and Rat Training TC0950 - Lab Safety
Haz Waste TC0016 - Safe Use of Formaldehyde TC0509 - Bio Safety/Bloodborne Pathogen
TC1550 - Rodent Surgery TC1200 - Mouse Wetlab TC0550 - Barrier Training TC2200 -
Hands-on Rodent Surgery TC2750 - Rodent Anesthesia TC0502 - Controlled Substances
Student will need to obtain occupational health clearance from Workforce Health&Safety.
Student will need to attend an IACUC Regulations Lecture. (See IACUC website for
schedule.) Student will need to obtain access to Black Barrier Facility 18 and 19.
• Background reading: Provided upon request
• Number of students: 2 students
• Location: P&S 8-508 (located in the rear hallway of Black Building)
• Additional information: Provided upon request

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