Summer & Fall 2015
http://ibp.med.uth.tmc.edu/
Scientists discover electrical control of
cancer cell growth
Rob Cahill, UTHealth Media Relations
With the aid of a high-powered electron microscope, UTHealth’s
John Hancock, M.B., B.Chir, Ph.D., ScD, left, and Yong Zhou,
Ph.D., are studying what causes cancer at the molecular level.
The molecular switches regulating human cell growth do a great
job of replacing cells that die during the course of a lifetime. But
when they misfire, life-threatening cancers can occur. Research led
by scientists at UTHealth has revealed a new electrical mechanism
that can control these switches.
This information is seen as critical in developing treatments for
some of the most lethal types of cancer including pancreatic, colon
and lung, which are characterized by uncontrolled cell growth
caused by breakdowns in cell signaling cascades.
The research focused on a molecular switch called K-Ras. Mutated
versions of K-Ras are found in about 20 percent of all human
cancers in the United States and these mutations lock the K-Ras
switch in the on position.
Initial work was done with human and animal cells and findings
were subsequently confirmed in a fruit fly model on membrane
organization.
“This has huge implications for biology,” Hancock said. “Beyond
the immediate relevance to K-Ras in cancer, it is a completely new
way that cells can use electrical charge to control a multitude of
signaling pathways, which may be particularly relevant to the
nervous system.”
“When K-Ras is locked in the on position, it drives cell division,
which leads to the production of a cancer,” said John Hancock,
M.B., B.Chir, Ph.D., ScD, the study’s senior author and chairman
of the Department of Integrative Biology and Pharmacology at
UTHealth Medical School. “We have identified a completely new Hancock’s co-authors at UTHealth include Ching-On Wong
molecular mechanism that further enhances the activity of K-Ras.” Ph.D., Kwang-Jin Cho, Ph.D., Dharini van der Hoeven, Ph.D.,
Findings appear in Science, a journal of the American Association Hong Liang, M.D., Dhananjay Thakur, Jialie Luo, Ph.D., Michael
Zhu, Ph.D., Hongzhen Hu, Ph.D., and Kartik Venkatachalam,
for the Advancement of Science.
Ph.D.
The study focused on the tiny electrical charges that all cells carry
across their limiting (plasma) membrane. “What we have shown is Co-authors from The University of Arizona include Milos Babic,
Ph.D., and Konrad Zinsmaier Ph.D.
that the electrical potential (charge) that a cell carries is inversely
proportional to the strength of a K-Ras signal,” Hancock said.
At UTHealth Medical School, Hancock is the vice dean for basic
With the aid of a high-powered electron microscope, the
investigators observed that certain lipid molecules in the plasma
membrane respond to an electrical charge, which in turn amplifies
the output of the Ras signaling circuit. This is exactly like a
transistor in an electronic circuit board.
Yong Zhou, Ph.D., first author and assistant professor of
integrative biology and pharmacology at UTHealth Medical
School, said, “Our results may finally account for a long-standing
but unexplained observation that many cancer cells actively try to
reduce their electrical charge.”
1
research, executive director of the Brown Foundation Institute of
Molecular Medicine for the Prevention of Human Diseases and
holder of the John S. Dunn Distinguished University Chair in
Physiology and Medicine.
Hancock and Venkatachalam are on the faculty of The University
of Texas Graduate School of Biomedical Sciences at Houston.
The study, titled “Membrane potential modulates plasma
membrane phospholoipid dynamics and K-Ras signaling,” was
supported by the Cancer Prevention & Research Institute of Texas
(RP130059) and National Institutes of Health (R01NS081301).
Integrative Biology & Pharmacology
Summer & Fall 2015
Faculty Spotlight
Schonbrunn gives invited lecture in Ether Dome
Dr. Agnes Schonbrunn
Dr. Agnes Schonbrunn, Ph.D. Professor in the Department of
Integrative Biology and Pharmacology was invited to give the 16th
Annual Nicholas T. Zervas, MD Lectureship at the Massachusetts
General Hospital, Harvard University on May 19, 2015. This
lectureship was established in honor of Nicholas T. Zervas MD, who
was the Chief of Neurosurgical Service, Massachusetts General
Hospital and the Higgins Professor of Neurosurgery, Harvard
Medical School from 1976 until he retired in 2000. Dr. Zervas made
many important original contributions to the understanding and
treatment of pituitary tumors and cerebral vasospasm, authoring
more than 260 publications. Dr. Schonbrunn was honored for her
fundamental contributions to understanding the action of
somatostatin receptors to regulate neuroendocrine tumor secretion
and to providing fundamental knowledge facilitating the
development of drugs targeting these receptors. The title of Dr.
Schonbrunn’s seminar was: Somatostatin Receptors as Therapeutic
Targets: The promise, the limitations, and the opportunities.
The presentation took place in the Ether Dome at Massachusetts General Hospital, which is known as the place where general anesthesia
was demonstrated for the first time. Dr. Schonbrunn’ seminar was hosted by Anne Klibanski, M.D. Laurie Carrol Guthart Professor of
Medicine, Harvard Medical School, Chief Academic Officer, and Harvard Medical School Dean for Academic Programs, Partners
HealthCare, and Chief, Neuroendocrine Unit , Massachusetts General Hospital.
Congratulations to Dr. Agnes
Schonbrunn on her appointment to
Vice-Chair for the Department of
Integrative Biology and Pharmacology
at the University of Texas Health
Science Center at Houston. Dr.
Schonbrunn’s term will begin on
October 1, 2015.
IN THIS
ISSUE
2
FACULTY
SPOTLIGHT
2
DEPARTMENTAL
NEWS & EVENTS
3
POSTDOC
STUDENT
7
Integrative Biology & Pharmacology
RESEARCH
CORNER
13
CALENDAR
18
Summer & Fall 2015
Departmental News & Events
Dessauer and Walters Collaboration
Dr. Carmen Dessauer
The IBP Newsletter is published
quarterly by the department and
distributed to faculty, staff and
students.
An electronic copy is
available on the IBP website at
http://ibp.med.uth.tmc.edu/
Chair, IBP
Dr. John Hancock
For many spinal cord injury (SCI) patients, their number one complaint is not confinement
to a wheel chair or the inability to walk, but rather is pain. Chronic pain of all kinds takes a
staggering toll on the American populace, affecting at least 116 million adults and costing
up to $635 billion annually in treatment and lost productivity. Although chronic pain
caused by spinal cord injury (SCI) represents a small fraction of this total, at least half of
all SCI patients endure life-long pain that resists available treatments. The mechanisms
that maintain any form of chronic pain (lasting months to a lifetime) remain mysterious,
which helps explain the limited effectiveness of current treatments for chronic pain. This
joint project will define mechanistic changes that occur in sensory neurons that contribute
to chronic pain after spinal cord injury. It will follow up on the discovery that spinal cord
injury causes a large number of these sensory neurons near and below the site of injury
to change from their normal state of electrical silence into a persistent state of
spontaneous activity. Preliminary data shows that agents that target cyclic AMP signaling
pathways decrease spontaneous activity and thus offer future promise for treating this
and other forms of chronic pain.
CRC Press
Dr. Xiaodong Cheng
Dr. Xiaodong Cheng has edited a book for CRC Press
with Dr. Michael Zhu as the Series Editor. Additional
authors contributed to the book from the Department
of Integrative Biology and Pharmacology include Drs.
Carmen Dessauer, Yong Li, and Fang Mei.
Book Title: Cyclic Nucleotide Signaling
Publisher: CRC Press
ISBN: 9781482235562
CAT# K23066
Web Link: https://www.crcpress.com/Cyclic-Nucleotide
-Signaling/Cheng/9781482235562
Vice Chair, IBP
Dr. Agnes Schonbrunn
Director of Management Operations
Monica Gardner
Editor
Catrina Stevens
Please contact any of our dedicated
staff for whatever assistance you may
require:
Catrina Stevens
Senior Administrative Coordinator
Catrina.M.Stevens@uth.tmc.edu
713.500.7536
Cordelia Conley
Senior Administrative Coordinator
Cordelia.P.Conley@uth.tmc.edu
713.500.7459
Deborah Brougher
Sr. Contracts & Grants Specialist
Deborah.Brougher@uth.tmc.edu
713.500.6322
Lisa Byrd
Senior Administrative Coordinator
Lisa.Byrd@uth.tmc.edu
713.500.7508
Monica Gardner
Director, Management Operations
Monica.Gardner@uth.tmc.edu
713.500.7516
Naomi Pinkney
Sr. Executive Assistant
Naomi.Pinkney@uth.tmc.edu
713.500.7547
Sandy Cegielski
Senior Administrative Coordinator
Sandy.Cegielski@uth.tmc.edu
713.500.7514
Trish McFarland
Coordinator II, Educational Programs
Patricia.McFarland@uth.tmc.edu
713.500.5470
Dr. Rebecca Berdeaux was appointed to the American Diabetes
Association Research Grant Review Committee for a three year term
(January 1, 2015—December 31, 2017). Core Research and Core
Development award applications undergo two rounds of peer review.
Score results from Preliminary Review determine whether or not an
application is promoted to Final Review. Approximately 20-25% of
submitted applications advance to Final Review. Applications that advance
to Final Review are discussed at the live Research Grant Review
Committee meeting. In the event a funded award is relinquished
throughout the course of the year, an award may be granted to an
application from Final Review that initially was not selected for funding.
3
Integrative Biology & Pharmacology
Summer & Fall 2015
Departmental News & Events
Dr. Li Receives New Grant—Intramuscular
Mechanisms of Cancer Cachexia
Dr. Yi-Ping Li
Cancer-induced cachexia
(cancer cachexia) is a wasting
syndrome featuring progressive
loss of muscle mass (muscle
wasting) due largely to excessive
proteolysis. Afflicting ~50% of
all cancer patients, cancer
cachexia is the immediate cause
of ~1/3 of all cancer-related
deaths. However, there is no
FDA-approved treatment for
cancer cachexia due to the poor
understanding of its etiology. A
hallmark of cancer cachexia is
the dramatic loss of myofibrillar
proteins. The ubiquitin-proteasome pathway plays a major role in
the loss of myofibrillar proteins in various forms of muscle atrophy
by targeting myofibrillar proteins for degradation via specific E3
ubiquitin ligases. Currently, cancer-induced muscle wasting is
widely thought to share common intracellular mechanisms with
other types of muscle atrophy. For example, elevated E3 ligase
MuRF1 is considered central for ALL forms of muscle atrophy
including cancer cachexia. In addition, the Akt-FoxO1/3 signaling
pathway is thought critical for ALL forms of muscle atrophy
because it regulates MuRF1 expression. However, recent data
revealed that cancer-induced muscle wasting appears to involve
unique intracellular mechanisms distinct from muscle atrophy
induced by physiological stress such as fasting, disuse or
denervation. Emerging evidence suggests that MuRF1
upregulation and the Akt-FoxO1/3 signaling pathway are nonessential for cancer-induced muscle wasting in animal models as
well as human patients. Instead, we found that an inflammationactivated signaling pathway involving p38 MAKP activation of
transcription factor C/EBPb is responsible for the bulk of muscle
protein degradation in a mouse cancer cachexia model. In
contrast, MuRF1 and FoxO1/3 are not responsible for the muscle
wasting in this model. Further, we found that C/EBPb
upregulates a previously overlooked E3, UBR2, in response to a
tumor burden. UBR2 is a member of an E3 ligase family that
serves as the substrate recognition components of the N-end rule
pathway that accounts for a large portion of total protein
ubiquitylation and ATP-dependent degradation of muscle proteins
induced by various catabolic stimuli. Within this E3 family, UBR2
is uniquely upregulated in the muscle of tumor-bearing rodents.
Thus, in this project we propose to test the hypothesis using cell
culture and mouse models of cancer cachexia that UBR2 is a key
E3 responsible for the excessive loss of myofibrillar proteins in
cancer cachexia, and by elucidating detailed signaling mechanisms
that mediate UBR2 upregulation in cancer cachexia we will test
experimental therapy to ameliorate muscle wasting by targeting the
signaling mechanisms. In addition, we will collaborate with a
clinical scientist to collect and examine samples from cancer
patients to determine whether human data support our hypotheses.
The Venkatachalam lab receives new grant!
Kartik Venkatachalam
Dr. Venkatachalam secured a grant from the Penn Orphan Disease Center
to extend their findings from the fly model of the childhood-onset
neurodegenerative disease, Mucolipidosis type IV (MLIV) model into a
mouse model of the disease. The goal of this project will be to test concepts
for treating this devastating childhood disease.
4
Integrative Biology & Pharmacology
Summer & Fall 2015
Departmental News & Events
Venkatachalam Lab featured in Batten Blog
Kartik Venkatachalam
The Venktatachalam Lab published a paper titled “Diminished
MTORC1-Dependent JNK-Activation Underlies the Neurodevelopmental Defects Associated with Lysosomal Dysfunction.” This
paper was featured in a blog focused on Batten Disease
http://battenblog.com/2015/10/30/bbdf-funded-researcherpublished-in-cell-reports/
New Members of the Team
Amit Gupta
Nabina Paudyal
William Robichaux
Suparna Sarkar
Postdoctoral Research
Fellow
GSBS Garduate
Research Assistant
Postdoctoral Research
Fellow
Postdoctoral Research
Fellow
Dr. Gorfe
Dr. Gorfe
Dr. Cheng
Dr. Gorfe
5
Integrative Biology & Pharmacology
HoangAnh Doan
Research Assistant I
Dr. Li
Summer & Fall 2015
Departmental News & Events
2015 Tour de Pink
On Sunday September 20th at 7 AM seven IBP cyclists began the Tour de Pink, an annual bike ride to raise funds for breast cancer
awareness and treatment for women in the greater Houston area. This is the fourth year in a row that IBP has participated in this
event. The IBP team consisted of Agi Schonbrunn, David Steffen, Dick Clark, Dmitry Akhmedov, Tanya Baldwin, Janani (Jan)
Subramaniam, and Shane Cunha. While each rider is expected to raise $125, we raised $1800 with Dick Clark securing the top fundraiser
award ($700). Both Tanya and Jan are recognized for their dedication for completing the 100 mile course in a sweltering 98°F.
6
Integrative Biology & Pharmacology
Summer & Fall 2015
Postdoc & Student Activities
New Postdoctoral and Student Fellowships
Dmitry Akhmedov Receives AHA Fellowship
Promotion of skeletal muscle regeneration through cAMP signaling
In Duchenne muscular dystrophy muscle fibers lack dystrophin, one of the structural proteins of
cytoskeleton, and are prone to degeneration. Currently there is no cure for muscular dystrophies.
Treatment with agonists for different cAMP-inducing G-protein coupled receptors, such as βadrenergic receptors, increases muscle mass and strength in patients with Duchenne muscular
dystrophy but cannot be used as therapy as it causes cardiovascular complications.
We hypothesize that enhancing cAMP signaling specifically in satellite cells and adult myofibers will
promote muscle regeneration after injury and improve muscle phenotype of Duchenne muscular
dystrophy. To directly test these hypotheses in vivo we have generated knock-in mice to accomplish
tissue-specific expression of an engineered GαS-protein coupled receptor (DREADD or Designer
Receptor Exclusively Activated by Designer Drug) which upon activation with an otherwise inert
agonist, clozapine N-oxide (CNO), specifically enhances cAMP production. We will use genetic
approach to selectively enhance cAMP signaling in satellite cells and myofibers. We expect that this work will result in better
understanding of cAMP functions in skeletal muscle regeneration and can potentially lead to development of therapies to improve
mobility of patients with Duchenne muscular dystrophy.
Arzu Ulu Receives CPRIT Fellowship
In Dr Frost's laboratory, we are elucidating mechanisms governing breast cancer cell motility. For my
CPRIT postdoctoral fellowship training program, I will identify mechanisms of how changes in
subcellular localization of a RhoA guanine nucleotide exhange factor, Net1A mediates breast cancer cell
motility and invasion. In specific, we will focus on epidermal growth factor (EGF) stimulated Net1A
relocalization in the cytosolic compartment of the breast cancer cells. As part of the fellowship
training, we will apply innovative methods and tools to generate creative and resourceful ideas.
Kelsey Maxwell Receives Rosalie B. Hite Fellowship
Kelsey Maxwell’s proposal focuses on two small GTPases, Ras and Rac1, that have been implicated in cancer
development and metastasis, and therefore show promise as lucrative drug targets. Her proposal addresses
some of the questions that remain regarding Ras and Rac1 signaling with respect to the plasma membrane.
For example, determining the specific lipids important for Rac1 nanocluster formation and signaling, or
whether Rac1 and Ras influence one another's signaling through ripple effects within the spatial segregation
of plasma membrane proteins and lipids. She hopes to identify a mechanism for the regulation of Rac1 and
Ras, and how plasma membrane interactions directly influence their function and role in tumor formation
and metastasis. The data may ultimately lead to novel and innovative strategies for targeting Rac/Ras-related
cancers.
7
Integrative Biology & Pharmacology
Summer & Fall 2015
Postdoc & Student Activities
Mykola Mamenko Receives AHA Fellowship
In July 2015 Dr. Mamenko received a Scientist Development Grant from the American Heart
Association, providing support for his research in 2015-2019. Mykola’s project investigates the role of
store-operated calcium entry in vasopressin-dependent water reabsorption in the collecting duct (CD).
Vasopressin-regulated water transport in the CD is a critical determinant of bodily fluid homeostasis.
Inability of CD cells to properly respond to vasopressin results in a devastating disorder –
nephrogenic diabetes insipidus (NDI). AVP acts on the cells of the CD, promoting fusion of the
vesicles containing water channels with the plasma membrane exposed to the forming urine. Both,
vesicle fusion and water transport in the CD, require a prolonged intracellular Ca2+ elevation, likely
achieved via a process called capacitative Ca2+ entry (CCE). While physiological relevance of
vasopressin-induced calcium signal in the CD remains enigmatic, numerous NDI cases lack a
recognized environmental or genetic mechanism of disease. Dr. Mamenko’s research reveals the
significance of CCE in vasopressin-dependent renal water handling, uncovering a novel mechanism
of underlying NDI pathology and aims to provide a new strategy to treat the disease.
Randi Fitzgibbon receives 2015 Dean’s Research Award
Recipients of the 2015 Dean’s Research Award were honored during a ceremony hosted by the Graduate Student Education Committee
Sept. 16, 2015, in the Medical School Fifth Floor Gallery.
From front left, Cihan Mehmet Kadipasaoglu; Heather Danhof; Katie McCallum; and Natoya Pearl. From back left, Dr. Jeff Frost,
emcee; Monica Gireud; Drew Dolino; William O'Brien; Randi Stewart; and Kaiqi Sun.
8
Integrative Biology & Pharmacology
Summer & Fall 2015
Postdoc & Student Activities
Excellence in Research
Winners of the 2015 Dean’s Excellence in
Research Award for Postdoctoral Fellows are,
from left, Dr. Ching On Wong, second place,
mentored by Dr. Kartik Venkatachalam,
Department of Integrative Biology and
Pharmacology; Dr. Yanning Rui, first place,
mentored by Dr. Sheng Zhang, Institute of
Molecular Medicine; and Dr. Mykola
Mamenko, third place, mentored by Dr. Oleh
Pochynyuk, Department of Integrative Biology
and Pharmacology.
Kelsey Maxwell (second from left) and
Randi Fitzgibbon (middle) competed in
the John P. McGovern competition The
competition was an oral presentation
competition for GSBS students based on
their current research projects. They
were chosen after an application process
and invited to give a ten-minute
presentation and respond to questions
before a panel of judges composed of
GSBS faculty at a public
symposium. Congratulations to Randi
for winning 3rd place!
Ms. Laura Vandellar, a 2015 graduating medical student,
received the G. Alan Robison award for the best
performance in medical pharmacology, 2012-2013. Dr.
Robison, who just recently passed away, was the 1972
founding chair of the UT Medical School department of
pharmacology. Al, as he was called, emphasized from the
outset the importance of quality teaching by his faculty. He
also was the principal author of "Cyclic AMP," a ground
breaking work with Dr. Robert W. Butcher and Dr. Earl W.
Sutherland, Jr. who won the 1971 Nobel Prize in Physiology
or Medicine.
9
Integrative Biology & Pharmacology
Summer & Fall 2015
Postdoc & Student Activities
Vaidehi and Team win First Place!
Vaidehi Thanawala
Baylor Global Innovation Center organized the
first Global Health Hackathon on September 19th20th at the TMC accelerator to help bring innovative technology solutions for low-resource settings
around the world. The Endoscopic Hackers team
comprising of Vaidehi Thanawala (UTHealth),
Suganya Karunakaran (UTHealth), Philip Levine
(BCM), Paul Hausknecht (BCM), Andy Zhang
(Rice University) and Aunj Marathe (Baylor University) won the first place for their prototype lowcost, highly innovative endoscope with banding
capacity- The Hackascope. The Hackascope was
designed at a cost of ~$60, whereas regular endoscope equipment currently costs around $30,000.
In addition to the low cost, the other major advantage of the Hackascope is that it is operated via
a USB port making the Hackascope highly portable and easy to use in low-resource settings.
Congratulations!
Congratulations to
Dhananjay Thakur
(Left)
and
Henry Wu (Right)
for successfully
defending their
thesis!
10
Integrative Biology & Pharmacology
Summer & Fall
Banerjee U, Cheng X. Exchange protein directly activated by cAMP encoded by the mammalian rapgef3 gene:
Structure, function and therapeutics. Gene. 2015 Oct 10;570(2):157-67. doi: 10.1016/j.gene.2015.06.063. Epub
2015 Jun 26.
Brand CS, Sadana R, Malik S, Smrcka AV, Dessauer CW. Adenylyl Cyclase 5 Regulation by Gβγ Involves IsoformSpecific Use of Multiples Interation Sites. Mol Pharmacol. 2015 Oct;88(4):758-67. doi: 10.1124/mol.115.099556.
Epub 2015 Jul 23.
Cho KJ, van der Hoeven D, Zhou Y, Maekawa M, Ma X, Chen W, Fairn GD and Hancock JF (2015), Inhibition of
acid sphingomyelinase by fendiline depletes cellular phosphatidylserine and mislocalizes K-Ras from the plasma
membrane. Mol Cell Biol. 2015 Nov 16. pii: MCB.00719-15. [Epub ahead of print].
Dial EJ, Dawson PA, Lichtenberger LM. In vitro evidence that phosphatidylcholine protects against indomerthacin/
bile acid-induced injury to cell. Am J Physiol Gastrointest Liver Physiol. 2015 Feb 1;308(3):G217-22. doi: 10.1152/
ajpgi.00322.2014. Epub 2014 Dec 4.
Ganesan L, Levental I. Pharmacological Inhibition of Protein Lipidation. J Membr Biol. 2015 Dec;248(6):929-41.
doi: 10.1007/s00232-015-9835-4. Epub 2015 Aug 18.
Hoover RS, Tomilin V, Hanson LN, Pochynyuk O, Ko B. PTH Modulation of NCC Activity Regulates TRPV5 Calcium
Reabsorption. Am J Physiol Renal Physiol. 2015 Nov 25: [Epub ahead of print].
Publications
Ihida-Stansbury K, Ames J, Chokshi M, Aiad N, Sanyal S, Kawabata KC, Levental I, Sundararaghavan HG,
Burdick JA, Janmey P, Miyazono K, Wells RG, Jones PL. Role played by Prx1-dependent extracellular matrix
properties in vascular smooth muscle development in embryonic lungs. Pulm Circ. 2015 Jun;5(2):382-97. doi:
10.1086/681272.
Li Z, Gorfe AA. Receptor-mediated membrane adhesion of lipid–polymer hybrid (LPH) nanoparticles studied by
dissipative particle dynamics simulations. Nanoscale. 2015 Jan 14;7(2):814-24. doi: 10.1039/c4nr04834b.
Lichtenberger LM, Bhattari D, Phan, TM. Dial EJ, Uray K. Supression of contractile activity in the small
intesetine by indomethacin and omeprazole. Amer J Physiol Gastrointest Liver Physiol. 2015 May 1;308(9):G785-93.
doi: 10.1152/ajpgi.00458.2014. Epub 2015 Feb 26.
Lin X, Li Z, Gorfe AA. Reversibility of the effects of peptide concentration and lipid composition on the clustering of H
-Ras lipid anchors. Biophys J. 2015 Dec 15;109(12):2467-70. doi: 10.1016/j.bpj.2015.11.009.
Lorent JH, Levental I. Structural determinants of protein partitioning into ordered membrane domains and lipid rafts.
Chem Phys Lipids. 2015 Aug 1. pii: S0009-3084(15)30027-X. doi: 10.1016/j.chemphyslip.2015.07.022. [Epub ahead
of print].
Mamenko M, Dhande I, Tomilin V, Zaika O, Boukelmoune N, Zhu Y, Gonzalez-Garay ML, Pochynyuk O, Doris
PA. Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus.J Am Soc Nephrol.
2015 Nov 16. pii: ASN.2014121200. [Epub ahead of print].
McCarthy M, Prakash P, Gorfe AA. Computational Allosteric Ligand Binding Site Identification on Ras Proteins. Acta
Biochim Biophys Sin (Shanghai). 2015 Oct 19. pii: gmv100. [Epub ahead of print].
Najumudeen AK, Posada IMD, Lectez B, Zhou Y, Landor S, Fallarero A, Vuorela P, Hancock JF, Abankwa D
(2015), Phenotypic screening identifies protein synthesis inhibitors as H-ras-nanocluster dependent tumor growth
inducers. Biochemistry. 2015 Nov 30. [Epub ahead of print]
Pavlov TS, Ilatovskaya DV, Palygin O, Levchenko V, Pochynyuk O, Staruschenko A. Implementing Patch Clamp
and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium. J Vis Exp.
2015 Sep 1;(103). doi: 10.3791/53035.
Piktel E, Niemirowicz K, Wnorowska U, Wątek M, Wollny T, Głuszek K, Góźdź S, Levental I, Bucki R. The Role of
Cathelicidin LL-37 in Cancer Development. Arch Immunol Ther Exp (Warsz). 2015 Sep 22. [Epub ahead of print]
Prakash P, Hancock JF, Gorfe AA. Binding hotspots on K-Ras: consensus ligand binding sites and other reactive
regions from probe-based molecular dynamics analysis. Proteins. 2015 May;83(5):898-909. doi: 10.1002/prot.24786.
Epub 2015 Mar 25.
Prakash P, Sayyed-Ahmad A, Gorfe AA. pMD-membrane: A method for the identification of ligand binding
sites on membrane-bound proteins. PLoS Comput Biol. 2015 Oct 27;11(10):e1004469. doi: 10.1371/
journal.pcbi.1004469. eCollection 2015.
11
Integrative Biology & Pharmacology
Summer & Fall
Prakash P, Zhou Y, Liang H, Hancock JF, Gorfe AA (2015), Oncogenic K -Ras on membrane: Stick, Swing
and Rock. Submitted.
Schonbrunn A. Invited Editorial: Reproducibility in Research: A cautionary Tale and Lessons Not Learned .
Mol Endocrinol. 2015 Sep;29(9):1219-21. doi: 10.1210/me.2015-1209.
Schwede F, Chepurny OG, Kaufholz M, Bertinetti D, Leech CA, Cabrera O, Zhu Y, Mei F, Cheng X, Manning Fox
JE, MacDonald PE, Genieser HG, Herberg FW, Holz GG. Rp-cAMPS Prodrugs Reveal the cAMP Dependence of
First-Phase Glucose-Stimulated Insulin Secretion. Mol Endocrinol. 2015 Jul;29(7):988-1005. doi: 10.1210/me.20141330. Epub 2015 Jun 10.
Solman S, Ligabue A, Blazevits O, Jaiswal A, Zhou Y, Liang H, Lectez B, Kopra K, Guzman C, Harma H, Hancock
JF, Aittokallio T and Abankwa D (2015), Specific cancer associated mutations in the switch III-region of Ras
increase tumorigenicity by nanocluster augmentation. Elife. 2015 Aug 14;4. doi: 10.7554/eLife.08905.
Timsah Z, Ahmed Z, Ivan C, Berrout J, Gagea M, Zhou Y, Pena G, Hu X, Vallien C, Kingsley C, Lu Y, Hancock JF,
Liu J, Gladden A, Mills G, Lopez-Berestein G, Hung MC, Sood A, Bogdanov M and Ladbury J (2015), Grb2
depletion under non-stimulated conditions inhibits PTEN, promotes Akt-induced tumor formation and contributes to
poor prognosis in ovarian cancer. Oncogene. 2015 Jul 27. doi: 10.1038/onc.2015.279. [Epub ahead of print].
Publications
Tomilin V, Mamenko M, Zaika O, Pochynyuk O. Role of renal TRP channels in physiology and pathology. Semin
Immunopathol. 2015 Sep 18. [Epub ahead of print].
Wong CO, Palmieri M, Li J, Akhmedov D, Chao Y, Broadhead GT, Zhu MX, Berdeaux R, Collins CA, Sardiello M,
and Venkatachalam K. (2015) Diminished MTORC1-Dependent JNK-Activation Underlies the Neurodevelopmental
Defects Associated with Lysosomal Dysfunction. Cell Rep. 2015 Sep 29;12(12):2009-20. doi: 10.1016/
j.celrep.2015.08.047. Epub 2015 Sep 17.
Wolfe AR, Debeb BG, Lacerda L, Larson R, Bambhroliya A, Huang X, Bertucci F, Finetti P, Birnbaum D, Van Laere
S, Diagaradjan P, Ruffell B, Trenton NJ, Chu K, Hittelman W, Diehl M, Levental I, Ueno NT, Woodward WA.
Simvastatin prevents triple-negative breast cancer metastasis in pre-clinical models through regulation of FOXO3a.
Breast Cancer Res Treat. 2015 Dec;154(3):495-508. doi: 10.1007/s10549-015-3645-3. Epub 2015 Nov 21.
Wu HC, Yamankurt G, Luo J, Subramaniam J, Hashmi SS, Hu H, Cunha SR. Identification and characterization of
two ankyrin-B isoforms in mammalian heart. Cardiovasc Res. 2015 Sep 1;107(4):466-77. doi: 10.1093/cvr/cvv184.
Epub 2015 Jun 24.
Xie K, Masuho I, Shih CC, Cao Y, Sasaki K, Lai CW, Han PL, Ueda H, Dessauer CW, Ehrlich ME, Xu B, Willardson
BM, Martemyanov KA. Stable G protein-effector complexes in striatal neurons: mechanism of assembly and role in
neurotransmitter signaling. Elife. 2015 Nov 27;4. pii: e10451. doi: 10.7554/eLife.10451.
Yakubovich D, Berlin S, Kahanovitch U, Rubinstein M, Farhy-Tselnicker I, Styr B, Keren-Raifman T, Dessauer CW,
Dascal N. A Quantitative Model of the GIRK1/2 Channel Reveals That Its Basal and Evoked Activities Are
Controlled by Unequal Stoichiometry of Gα and Gβγ. PLoS Comput Biol. 2015 Nov 6;11(11):e1004598. doi:
10.1371/journal.pcbi.1004598. eCollection 2015.
Yamankurt G, Wu HC, McCarthy M, Cunha SR. Exon organization and novel alternative splicing of Ank3 in mouse
heart. PLoS One. 2015 May 29;10(5):e0128177. doi: 10.1371/journal.pone.0128177. eCollection 2015.
Ye N, Zhu Y, Chen H, Liu Z, Mei FC, Wild C, Chen H, Cheng X, Zhou J. Structure-Activity Relationship Studies of
Substituted 2-(Isoxazol-3-yl)-2-oxo-N'-phenyl-acetohydrazonoyl Cyanide Analogues: Identification of Potent
Exchange Proteins Directly Activated by cAMP (EPAC) Antagonists. J Med Chem. 2015 Aug 13;58(15):6033-47.
doi: 10.1021/acs.jmedchem.5b00635. Epub 2015 Jul 16.
Zaika O, Palygin O, Tomilin V, Mamenko M, Staruschenko A, Pochynyuk O. Insulin and IGF-1 activate
Kir4.1/5.1 channels in cortical collecting duct principal cells to control basolateral membrane voltage. Am J Physiol
Renal Physiol. 2015 Dec 2:ajprenal.00436.2015. doi: 10.1152/ajprenal.00436.2015. [Epub ahead of print].
Zhou Y, Hancock JF. (2015). Ras nanoclusters: versatile lipid-based signaling. Biochim Biophys Acta. 2015
Apr;1853(4):841-9. doi: 10.1016/j.bbamcr.2014.09.008. Epub 2014 Sep 16.
Zhou Y, Wong CO, Cho KJ, van der Hoeven D, Liang H, Thakur DP, Luo J, Babic M, Zinsmaier KE, Zhu MX,
Hu H, Venkatachalam K and Hancock JF (2015), Membrane potential modulates plasma membrane phospholipid
dynamics and K-Ras signaling. Science. 2015 Aug 21;349(6250):873-6. doi: 10.1126/science.aaa5619.
12
Integrative Biology & Pharmacology
Summer & Fall
Proposals & Awards
Deborah Brougher & Catrina Stevens
Sixteen proposals were submitted by the Department of Integrative
Biology & Pharmacology in the fourth quarter of Fiscal Year 2015 by Drs.
Gorfe, Cho, Cunha, Levental, Yue Li, Lichtenberger, Loose, Pochynyuk,
Schonbrunn, Walters, Yang, and Zuo.
Fourteen proposals were awarded this quarter. Faculty receiving new
awards include Drs. Berdeaux, Cheng, Cho, Dessauer, Levental, Li,
Lichtenberger, Mamenko, O’Neil, Pochynyuk, and Zhu.
~Data provided by Deborah Brougher, Sr. Grants and Contracts Specialist
Research Corner
Proposals Submitted FY2015 4th QTR
#
Submitted
11
5
16
Federal
Private
Total
10,044,510.00
10,044,510.00
1,138,000.00
10,044,510.00
1,138,000.00
1,455,917.00
0.00 11,182,510.00
Awards Received FY2015 4th QTR
# Rec'd
Federal
Private
8
4
2
2,278,101.00
14
2,278,101.00
State
245,244.00
Total
850,000.00
2,278,101.00
254,244.00
850,000.00
850,000.00
3,373,345.00
245,244.00
New Awards
New Awards received during the fourth quarter of Fiscal Year 2015 include:
Dr. Berdeaux. American Heart Association.
Promotion of Skeletal Muscle Regeneration
Through Camp Signaling.
Dr. Cheng. NIH. Novel Pharmacological Probes
Targeting Exchange Proteins Activated by Camp
(EPAC).
Dr. Dessauer. NIH. Mechanisms of Camp
Signaling that Drive Spontaneous Activity in
Nociceptors.
Dr. Levental. NIH. Lipidomic, Biophysical, and
Functional Differentiation of Mesenchymal Stem
Cell Membranes.
Dr. Levental. CPRIT. Membrane Structure and
Function in Oncogene Addiction.
Dr. Li. NIH. Identification of Key Tumor CellReleased Factors that Induce Cachexia.
Dr. Lichtenberger. United Stated Army. Use of
Topical PC-NSAIDS to Treat Burn Injury and Pain.
13
State
Dr. Mamenko. AHA. The Role of Capacitative
Calcium Entry in AVP-Dependent Water Transport
by the Kidney.
Dr. O’Neil. AHA. Regulation of Flow-induced K+
Wasting by the Collecting Duct.
Dr. Zhu. Proctor & Gamble Co.
Electrophysiological Examination of Select Personal
Health Care Actives on TRPA1.
Integrative Biology & Pharmacology
Summer & Fall
Proposals & Awards
Deborah Brougher & Catrina Stevens
Twenty five proposals were submitted by the Department of Integrative
Biology & Pharmacology in the first quarter of Fiscal Year 2016 by Drs.
Berdeaux, Chang, Dessauer, Du, Levental, Yue Li, Lichtenberger, Loose,
Venkatachalam, Walters, and Yang.
Seven proposals were awarded this quarter. Faculty receiving new
awards include Drs. Dessauer, Gorfe, Li, Lichtenberger, Pochynyuk, and
Yang.
~Data provided by Deborah Brougher, Sr. Grants and Contracts Specialist
Research Corner
Proposals Submitted FY2016 1st QTR
#
Submitted
19
2
Federal
Private
13,194,984.00
649,964.00
12,194,984.00
1,092,000
Total
13,194,984.00
1,092,000.00
1,092,000.00
4
25
State
649,964
649,964.00 14,936,948.00
Awards Received FY2016 1st QTR
# Rec'd
Federal
Private
6
1
1
1,209,644.00
7
1,209,644.00
State
2,000,000.00
1,209,604.00
11,480.00
2,000,000.00
2,000,000.00
3,221,124.00
11,480.00
11,480.00
Total
New Awards
New Awards received during the first quarter of Fiscal Year 2016 include:
Dr. Dessauer. U.S. Israel. Subunit CompositionDetermined Physiology of G1RK Channels.
Dr. Li. NIH. Intramuscular Mechanisms of Cancer
Caxhexia.
Dr. Lichtenberger. NIH. Surfactant Lipids and
Associated Proteins in Radiation-Induced Mucositis.
14
Integrative Biology & Pharmacology
Summer & Fall
IBP Seminar Series
~Directed by Drs. Ghislain Breton and Ilya Levental
September 21, 2015
October 26, 2015
John Hancock, MA, MB, BChir, PhD, ScD,
MRCP, FRACP
Integrative Biology and Pharmacology
University of Texas Medical School
Christopher M. Adams, M.D., Ph.D.
Internal Medicine & Molecular Physiology &
Biophysics
University of Iowa
Title of Talk: “ Ras signaling: electrics,
electronics and plasma membrane lipids”
Title of Talk: “Mechanisms and Treatment
of Age-related Skeletal Muscle Atrophy”
Host: Dr. Ghislain Breton
Host: Dr. Yi-Ping Li
November 2, 2015
September 28, 2015
Mark Dell’Acqua, Ph.D.
Pharmacology
University of Colorado
Juan Botas, Ph.D.
Molecular and Human Genetics
Baylor College of Medicine
Title of Talk: “Functional Analysis of
transcriptomic alterations in Huntington’s disease”
Host: Dr. Kartik Venkatachalam
Title of Talk: “ Coordination of Neuronal
cAMP and Calcium Signaling by an AKAP
Scaffold Protein”
Host: Dr. Carmen Dessauer
October 5, 2015
November 9, 2015
Meng Wang, Ph.D.
Molecular and Human Genetics
Baylor College of Medicine
Jeffrey Jacot, Ph.D.
Bioengineering
Rice University
Title of Talk: “LONGEVITY as a matter of
FAT”
Title of Talk: “ Engineered Heart Tissue for the
Correction of Heart Defects”
Host: Dr. Ilya Levental
Host: Dr. Guangwei Du
October 12, 2015
November 16, 2015
Eric Berglund, Ph.D.
Pharmacology
UTSouthwestern
Carmen Dessauer, Ph.D.
Integrative Biology and Pharmacology
University of Texas Medical School
Title of Talk: “Insulin-independent glucoregulatory mechanisms”
Host: Dr. Rebecca Berdeaux
Title of Talk: “ Anchored cyclic AMP
signaling: AC sensitization can be a pain”
Host: Dr. Ghislain Breton
October 19, 2015
November 23, 2015
George Eisenhoffer, Ph.D.
Department of Genetics
MD Anderson
Title of Talk: Visualizing Cell Turnover
During Epithelial Tissue Homeostasis and
Repair Using Developing Zebrafish
Host: Dr. Ghislain Breton
Yong Xu, M.D., Ph.D.
Molecular and Cellular Biology
Baylor College of Medicine
Title of Talk: “ Targeting Brain Serotonin 2C
Receptors for Binge Eating”
Host: Dr. Rebecca Berdeaux
Seminars are held on Mondays at 4:00 PM in MSB 2.135, unless otherwise noted. For information
and questions, please contact Catrina Stevens at catrina.m.stevens@uth.tmc.edu or
713-500-7536.
15
Integrative Biology & Pharmacology
Summer & Fall
IBP Seminar Series
~Directed by Drs. Ghislain Breton and Ilya Levental
November 30, 2015
January 25, 2016
Matthew Rasband, Ph.D.
Department of Neuroscience
Alan Smrcka, Ph.D.
Pharmacology and Physiology
University of Rochester Medical Center
Baylor College of Medicine
Title of Talk: “ The functional organization of
axons in health and disease”
Host: Dr. Qing Yang
Title of Talk: TBD
Host: Dr. Xiaodong Cheng
December 7, 2015
February 1, 2016
Haoqiang Ying, M.D., Ph.D.
Molecular and Cellular Oncology
MD Anderson
Patrick Dougherty, Ph.D.
Pain Medicine
MD Anderson Cancer Center
Title of Talk: “ Kras oncogene and the
maintenance of pancreatic cancer”
Host: Dr. Guangwei Du
Title of Talk: “ TLR4 interactions with
neuronal ion channels”
Host: Dr. Edgar T. Walters
December 14, 2015
February 8, 2016
Benjamin Shneider, M.D.
Pediatric Gastroenterology
Baylor College of Medicine
Jeffrey Petruska, Ph.D.
Anatomical Science & Neurobiology
Title of Talk: “ Potential Mechanisms and
Protean Clinical Manifestations of Defects in the
Aminophospholipid Flippase, ATP8B1 (Byler’s
Disease)”
Title of Talk: TBD
Host: Dr. Edgar T. Walters
Host: Dr. Lenard Lichtenberger
December 21, 2015
February 22, 2016
Gordon Mills, M.D., Ph.d.
Pediatric Gastroenterology
Baylor
Neal Silverman, Ph.D.
Department of Medicine
University of Massachusetts
Title of Talk: “A systems approach to
personalized medicine”
Host: Dr. Jeffrey Frost
Title of Talk: “ Responding on the Fly:
Innate immune recognition and signal
transduction in Drosophila”
January 11, 2016
February 29, 2016
Lauren Webb, Ph.D.
Department of Chemistry
University of Texas at Austin
Title of Talk: “Investigating Electrostatic
Mechanisms of Biomolecular Organization and
Function Through Vibrational Spectroscopy”
Host: Dr. Alemayehu Gorfe Abebe
Dihua Yu, M.D., Ph.D.
Molecular and Cellular Oncology
MD Anderson Cancer Center
Title of Talk: “ Defeating Cancer Metastasis
in the Era of Precision Medicine”
Host: Dr. Jeffrey Frost
Seminars are held on Mondays at 4:00 PM in MSB 2.135, unless otherwise noted. For information
and questions, please contact Catrina Stevens at catrina.m.stevens@uth.tmc.edu or
713-500-7536.
16
Integrative Biology & Pharmacology
Summer & Fall
IBP Calendar of Events
Dates to Remember:
CRB Meetings, 12-1 PM, Room 4.100
January 7, February 4, March 3, April 7,
May 5
CRB
December 18: IBP Holiday Party
December 21: First Day of Winter
December 24-January 1: Winter Holiday-December 2425 & January 1-The University will be closed for Official
Business; December 28-31 are skeleton crew holidays.
Faculty Coffee/Tea, 10-11 AM, MSB
4.100
January 18: Martin Luther King Day-The University will
be closed for Official Business
February 2: Groundhog Day
December 2, 9, 16, 23
January 6, 13, 20, 27
February 3, 10, 17, 24
March 2, 9, 16, 23, 30
April 6, 13, 20, 27
May 4, 11, 18, 25
STG Seminar, 4-5 PM, MSB 4.100
December 2, 9, 16
January 6, 13, 20, 27
February 3, 10, 17, 24
March 2, 9, 16, 23, 30
April 6, 13, 20, 27
May 4, 11, 18, 25
17
February 14: Valentine’s Day
February 15: Presidents’ Day-The University will be
closed for Official Business
March 17: St. Patrick’s Day
March 20: First Day of Spring
March 27: Easter
May 8: Mother’s Day
May 30: Memorial Day-The University will be closed for
Official Business
Integrative Biology & Pharmacology
Summer & Fall