1 Integrative Biology & Pharmacology Summer & Fall 2015

Summer & Fall 2015 https://med.uth.edu/ibp

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.

“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

molecular mechanism that further enhances the activity of K-Ras.”

Findings appear in Science, a journal of the American Association

for the Advancement of Science.

The study focused on the tiny electrical charges that all cells carry

across their limiting (plasma) membrane. “What we have shown is

that the electrical potential (charge) that a cell carries is inversely

proportional to the strength of a K-Ras signal,” Hancock said.

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.”

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.”

Hancock’s co-authors at UTHealth include Ching-On Wong

Ph.D., Kwang-Jin Cho, Ph.D., Dharini van der Hoeven, Ph.D.,

Hong Liang, M.D., Dhananjay Thakur, Jialie Luo, Ph.D., Michael

Zhu, Ph.D., Hongzhen Hu, Ph.D., and Kartik Venkatachalam,

Ph.D.

Co-authors from The University of Arizona include Milos Babic,

Ph.D., and Konrad Zinsmaier Ph.D.

At UTHealth Medical School, Hancock is the vice dean for basic

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).

2 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.

FACULTY

SPOTLIGHT 2 DEPARTMENTAL

NEWS & EVENTS 3 POSTDOC

STUDENT 7 RESEARCH

CORNER 13 CALENDAR 18 IN THIS

ISSUE

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.

3 Integrative Biology & Pharmacology Summer & Fall 2015

Departmental News & Events 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

https://med.uth.edu/ibp

Chair, IBP

Dr. John Hancock

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. 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

CRC Press Dr. Xiaodong Cheng

Dessauer and Walters Collaboration Dr. Carmen Dessauer

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.

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.

4 Integrative Biology & Pharmacology Summer & Fall 2015

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 non-

essential for cancer-induced muscle wasting in animal models as

well as human patients. Instead, we found that an inflammation-

activated 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.

Departmental News & Events

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.

The Venkatachalam lab receives new grant! Kartik Venkatachalam

5 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 Neurodevel-

opmental Defects Associated with Lysosomal Dysfunction.” This

paper was featured in a blog focused on Batten Disease.

Amit Gupta

Postdoctoral Research

Fellow

Dr. Gorfe

New Members of the Team

Nabina Paudyal

GSBS Garduate

Research Assistant

Dr. Gorfe

Suparna Sarkar

Postdoctoral Research

Fellow

Dr. Gorfe

William Robichaux

Postdoctoral Research

Fellow

Dr. Cheng

HoangAnh Doan

Research Assistant I

Dr. Li

6 Integrative Biology & Pharmacology 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.

7 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 β-

adrenergic 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.

8 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.

9 Integrative Biology & Pharmacology Summer & Fall 2015

Excellence in Research

Postdoc & Student Activities

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.

10 Integrative Biology & Pharmacology Summer & Fall

Postdoc & Student Activities

Congratulations!

Congratulations to Dhananjay Thakur

(Left) and

Henry Wu (Right) for successfully defending their

thesis!

Baylor Global Innovation Center organized the

first Global Health Hackathon on September 19th-

20th at the TMC accelerator to help bring innova-

tive 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 Uni-

versity) won the first place for their prototype low-

cost, highly innovative endoscope with banding

capacity- The Hackascope. The Hackascope was

designed at a cost of ~$60, whereas regular endo-

scope equipment currently costs around $30,000.

In addition to the low cost, the other major ad-

vantage of the Hackascope is that it is operated via

a USB port making the Hackascope highly porta-

ble and easy to use in low-resource settings.

Vaidehi and Team win First Place! Vaidehi Thanawala

11 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 Isoform-Specific 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].

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.

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12 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.2014-1330. 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].

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.

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13 Integrative Biology & Pharmacology Summer & Fall

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 Cell-

Released Factors that Induce Cachexia.

Dr. Lichtenberger. United Stated Army. Use of

Topical PC-NSAIDS to Treat Burn Injury and Pain.

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.

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

New Awards New Awards received during the fourth quarter of Fiscal Year 2015 include:

R

es

ea

rc

h C

or

ne

r

Proposals & Awards Deborah Brougher & Catrina Stevens

Proposals Submitted FY2015 4th QTR

#

Submitted Federal Private State Total

11 10,044,510.00 10,044,510.00

5 1,138,000.00 1,138,000.00

16 10,044,510.00 1,455,917.00 0.00 11,182,510.00

Awards Received FY2015 4th QTR

# Rec'd Federal Private State Total

8 2,278,101.00 2,278,101.00

4 245,244.00 254,244.00

2 850,000.00 850,000.00

14 2,278,101.00 245,244.00 850,000.00 3,373,345.00

14 Integrative Biology & Pharmacology Summer & Fall

Dr. Dessauer. U.S. Israel. Subunit Composition-

Determined Physiology of G1RK Channels.

Dr. Li. NIH. Intramuscular Mechanisms of Cancer

Caxhexia.

Dr. Lichtenberger. NIH. Surfactant Lipids and

Associated Proteins in Radiation-Induced Mucositis.

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

New Awards New Awards received during the first quarter of Fiscal Year 2016 include:

R

es

ea

rc

h C

or

ne

r

Proposals & Awards Deborah Brougher & Catrina Stevens

Proposals Submitted FY2016 1st QTR

#

Submitted Federal Private State Total

19 13,194,984.00 13,194,984.00

2 1,092,000.00 1,092,000.00

4 649,964.00 649,964

25 12,194,984.00 1,092,000 649,964.00 14,936,948.00

Awards Received FY2016 1st QTR

# Rec'd Federal Private State Total

6 1,209,644.00 1,209,604.00

1 11,480.00 11,480.00

1 2,000,000.00 2,000,000.00

7 1,209,644.00 11,480.00 2,000,000.00 3,221,124.00

15 Integrative Biology & Pharmacology Summer & Fall

IBP Seminar Series

September 21, 2015

John Hancock, MA, MB, BChir, PhD, ScD,

MRCP, FRACP

Integrative Biology and Pharmacology

University of Texas Medical School

Title of Talk: “ Ras signaling: electrics,

electronics and plasma membrane lipids”

Host: Dr. Ghislain Breton

October 26, 2015

Christopher M. Adams, M.D., Ph.D.

Internal Medicine & Molecular Physiology &

Biophysics

University of Iowa

Title of Talk: “Mechanisms and Treatment

of Age-related Skeletal Muscle Atrophy”

Host: Dr. Yi-Ping Li

September 28, 2015

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

November 2, 2015

Mark Dell’Acqua, Ph.D.

Pharmacology

University of Colorado

Title of Talk: “ Coordination of Neuronal

cAMP and Calcium Signaling by an AKAP

Scaffold Protein”

Host: Dr. Carmen Dessauer

October 5, 2015

Meng Wang, Ph.D.

Molecular and Human Genetics

Baylor College of Medicine

Title of Talk: “LONGEVITY as a matter of

FAT”

Host: Dr. Guangwei Du

November 9, 2015

Jeffrey Jacot, Ph.D.

Bioengineering

Rice University

Title of Talk: “ Engineered Heart Tissue for the

Correction of Heart Defects”

Host: Dr. Ilya Levental

October 12, 2015

Eric Berglund, Ph.D.

Pharmacology

UTSouthwestern

Title of Talk: “Insulin-independent gluco-

regulatory mechanisms”

Host: Dr. Rebecca Berdeaux

November 16, 2015

Carmen Dessauer, Ph.D.

Integrative Biology and Pharmacology

University of Texas Medical School

Title of Talk: “ Anchored cyclic AMP

signaling: AC sensitization can be a pain”

Host: Dr. Ghislain Breton

October 19, 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

November 23, 2015

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

~Directed by Drs. Ghislain Breton and Ilya Levental

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 Seminar Series

November 30, 2015

Matthew Rasband, Ph.D.

Department of Neuroscience

Baylor College of Medicine

Title of Talk: “ The functional organization of

axons in health and disease”

Host: Dr. Qing Yang

January 25, 2016

Alan Smrcka, Ph.D.

Pharmacology and Physiology

University of Rochester Medical Center

Title of Talk: TBD

Host: Dr. Xiaodong Cheng

December 7, 2015

Haoqiang Ying, M.D., Ph.D.

Molecular and Cellular Oncology

MD Anderson

Title of Talk: “ Kras oncogene and the

maintenance of pancreatic cancer”

Host: Dr. Guangwei Du

February 1, 2016

Patrick Dougherty, Ph.D.

Pain Medicine

MD Anderson Cancer Center

Title of Talk: “ TLR4 interactions with

neuronal ion channels”

Host: Dr. Edgar T. Walters

December 14, 2015

Benjamin Shneider, M.D.

Pediatric Gastroenterology

Baylor College of Medicine

Title of Talk: “ Potential Mechanisms and

Protean Clinical Manifestations of Defects in the

Aminophospholipid Flippase, ATP8B1 (Byler’s

Disease)”

Host: Dr. Lenard Lichtenberger

February 8, 2016

Jeffrey Petruska, Ph.D.

Anatomical Science & Neurobiology

Title of Talk: TBD

Host: Dr. Edgar T. Walters

December 21, 2015

Gordon Mills, M.D., Ph.d.

Pediatric Gastroenterology

Baylor

Title of Talk: “A systems approach to

personalized medicine”

Host: Dr. Jeffrey Frost

February 22, 2016

Neal Silverman, Ph.D.

Department of Medicine

University of Massachusetts

Title of Talk: “ Responding on the Fly:

Innate immune recognition and signal

transduction in Drosophila”

January 11, 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

February 29, 2016

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

~Directed by Drs. Ghislain Breton and Ilya Levental

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.

17 Integrative Biology & Pharmacology Summer & Fall

IBP Calendar of Events

CRB Meetings, 12-1 PM, Room 4.100

January 7, February 4, March 3, April 7,

May 5

Faculty Coffee/Tea, 10-11 AM, MSB

4.100

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

Dates to Remember:

December 18: IBP Holiday Party

December 21: First Day of Winter

December 24-January 1: Winter Holiday-December 24-

25 & January 1-The University will be closed for Official

Business; December 28-31 are skeleton crew holidays.

January 18: Martin Luther King Day-The University will

be closed for Official Business

February 2: Groundhog Day

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

CRB