People at Dr. Nathan Wall's lab
Principal Investigator
Nathan Wall, PhD, MBA, MS
Assistant Professor & Biochemistry, Graduate Program Director
Division of Biochemistry
nwall@llu.edu
Phone: (909) 558-4000 Ext. 81397
People
Arjun Ashok, MBBS
Volunteer Research Associate
Division of Biochemistry
Loma Linda University
Loma Linda, CA 92350
909-558-4000 (x81368)
aashok@llu.edu
Research Interests:
I am a voluntary research associate in Dr. Wall's lab. I am currently investigating the role of Survivin and other IAPs as plausible biomarkers for early detection of cancer. This project is a proteomic study that involves isolating exosomes from the serum of pancreatic cancer patients and utilizing Mass spectrometry for identification of proteins.
1. Khan S, Jutzy JMS, Valenzuela MMA, Turay D, Aspe JR, Ashok A, Mirshahidi S, Mercola D, Lilly MB, Wall NR. Plasma-Derived Exosomal Survivin, a Plausible Biomarker for Early Detection of Prostate Cancer. PLoS One, 2012. In Press.
Jonathan Aspe
7th Year Ph.D. Student
1st Year Medical Student
Division of Biochemistry
Loma Linda University
Loma Linda, CA 92350
909-558-4000 (x81368)
jaspe@llu.edu
Research Interests:
The purpose of my work was to determine if exosomes, collected from a melanoma cell line, built to harbor a tetracycline-regulated Survivin-T34A, contained the dominant negative and whether these exosomes could then affect pancreatic cancer cells in culture. We were able to show that exosomes collected in the absence of tetracycline (tet-off) from the engineered melanoma cells do contain Survivin T34A and when used alone or in combination with Gemcitabine, induced a significant increase in apoptotic cell death when compared to the Survivin-T34A exosome or Gemcitabine alone on a variety of pancreatic cancer cell lines. This exosomes/Survivin-T34A study showed that a new delivery method for anti-cancer proteins within the cancer microenvironment may prove useful in targeting cancers of the pancreas.
Selected peer-reviewed publications:
1. Khan S, Jutzy JMS, Aspe JR, Valenzuela MMA, Park J, Turay D, Wall NR. The Application of Membrane Vesicles for Cancer Therapy. Book 3, Advances in Cancer Therapy, InTech Publishing 2011, ISBN 978-953-307-703-1.
2. Khan S, Jutzy JMS, Valenzuela MMA, Turay D, Aspe JR, Ashok A, Mirshahidi S, Mercola D, Lilly MB, Wall NR. Plasma-Derived Exosomal Survivin, a Plausible Biomarker for Early Detection of Prostate Cancer. PLoS One, 2012. In Press.
3. Khan S, Jutzy JMS, Aspe JR, McGregor D, Neidigh JW, Wall NR. Survivin is released from cancer cells via exosomes. Apoptosis, 16(1): 1-12, 2011.
4. Aspe JR and Wall NR. Survivin-T34A: molecular mechanism and therapeutic potential. OncoTargets and Therapy, 3:247-254, 2010.
5. Galloway NR, Aspe JR, Sellers C, Wall NR. Enhanced antitumor effect of combined gemcitabine and proton radiation in the treatment of pancreatic cancer. Pancreas 38(7) 782-790, 2009.
6. Khan S, Aspe JR, Asumen MG, Almaguel F, Odumosu O, Acevedo-Martinez S, De Leon M, Langridge W, Wall NR. Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential. British Journal of Cancer 100(7):1073-1086, 2009.
Malyn May Asuncion Valenzuela, MS
4th Year Ph.D. Student
Division of Biochemistry
Loma Linda University
Loma Linda, CA 92350
909-558-4000 (x81368)
mmvalenzuela@llu.edu
Research Interests:
Our lab studies a family of proteins called the Inhibitor of Apoptosis proteins (IAP). Recently, our lab has shown that cancer cells shed Survivin, an IAP, via exosomes, which are small membrane vesicles. Release of Survivin into the extracellular space causes neighboring cancer cells to rapidly proliferate, acquire an increased potential to be invasive and become resistant to therapy. My project focuses on how patients with metastatic pancreatic cancer develop chemoresistance to Gemcitabine, the gold standard chemotherapy and how exosomal IAPs play a role in chemoresistance. In addition, I am also studying how Survivin is loaded onto exosomes.
Selected peer-reviewed publications:
1. Khan S, Jutzy JMS, Aspe JR, Valenzuela MMA, Park J, Turay D, Wall NR. The Application of Membrane Vesicles for Cancer Therapy. Cancer Treatment/Book 3, 2011, ISBN 979-953-307-209-7.
2. Jutzy, JMS, Khan S, Valenzuela MMA, Milford TM, Payne KJ, Wall NR. Tumor-released survivin inhibits T cell proliferation and alters CD4+ T cell cytokine profiles to induce a pro-tumor environment. Cancer Microenvironment, 2012
3 .Khan S, Jutzy JMS, Valenzuela MMA, Turay D, Aspe JR, Ashok A, Mirshahidi S, Mercola D, Lilly MB, Wall NR. Plasma-Derived Exosomal Survivin, a Plausible Biomarker for Early Detection of Prostate Cancer. PLoS One, 2012. In Press.
Carlos Diaz-Osterman
3rd Year Ph.D. Student
Division of Biochemistry
Loma Linda University
Loma Linda, CA 92350
909-558-4000 (x81368)
cdiazosterman@llu.edu
Research Interests:
My work focuses on the prevention of pancreatic cancer, with a current push towards the use of herbal derivate compounds. Two such compounds, 6-gingerol (a ginger root derivative) and curcumin (a turmeric derivative), have been show to induce cell death or inhibit proliferation of several types of tumors. Testing these results on the pancreatic cancer cell lines Panc1 and Mia Paca2, 6-gingerol and curcumin were analyzed on their ability to affect cell proliferation and survival. Also, the expression levels of important cell cycle proteins and the inhibitors of apoptosis (Survivin, XIAP, cIAP1 and cIAP2) were analyzed in the presence of 6-gingerol and curcumin to determine if the cell cycle was at all affected during treatment in the presence or absence of cell death. So far, our results make us optimistic that these two herbal derivatives will provide benefit to pancreatic cancer patients either alone or when combined with anti-metabolite agents such as gemcitabine.
Grace Esebanmen
2nd Year M.S. Student
Department of Biology
Loma Linda University
Loma Linda, CA 92350
909-558-4000 (x81368)
gesebanmen@llu.edu
Research Interests:
Very little is known about NK cell exosomes despite the importance of these cells in innate and adaptive immunity. My goal is to purify and identify NK exosomes and their content and determine if NK-derived exosomes carry the cytotoxic arsenal of granzyme B and could be used to determine the fate of cancer cells treated with them.
Heather Ferguson
3rd Year Ph.D. Student
Division of Biochemistry
Loma Linda University
Loma Linda, CA 92350
909-558-4000 (x81368)
hferguson@llu.edu
Research Interests:
My research interests are cancer biology and immunology. Currently, I am working on a project investigating the inhibitor of apoptosis (IAP) content of exosomes produced by lymphoma cells. I am especially interested if the IAP profile changes when the B cells are stressed or exposed to drugs, and ultimately hope to define an exosomal IAP signature with biomarker potential.
Nicholas Galloway
8th Year Ph.D. Student
4st Year Medical Student
Division of Biochemistry
Loma Linda University
Loma Linda, CA 92350
909-558-4000 (x81368)
ngalloway@llu.edu
Research Interests:
The purpose of my work was to investigate whether the putative stress response transcription factor Yin Yang 1 (YY1) was able to contribute to the upregulation of the inhibitor of apoptosis protein, Survivin. Surprisingly, when YY1 is overexpressed using a survivin promoter reporter system, luciferase expression was repressed 5-10 fold. YY1 involvement in survivin promoter repression was confirmed using siRNA directed against YY1. These studies showed that knockdown of YY1 releases the survivin promoter from the observed repression and leads to a 3-5 fold increase in promoter activity above basal levels. We then treated cells with thapsigargin, an inducer of ER stress and a known inducer of YY1, and saw that basal survivin promoter activity was decreased 8-fold. Collectively, these findings identify both basal and stress-induced transcriptional requirements of survivin gene expression which we hope to capitalize on therapeutically.
Selected peer-reviewed publications:
1. Galloway NR, Aspe JR, Sellers C, Wall NR. Enhanced antitumor effect of combined gemcitabine and proton radiation in the treatment of pancreatic cancer. Pancreas 38(7) 782-790, 2009.
2. Obenaus A, Robbins M, Blanco G, Galloway NR, Snissarenko E, Gillard E, Lee S, Currás-Collazo M. Multi-modal magnetic resonance imaging alterations in two rat models of mild neurotrauma. J. Neurotrauma 24(7) 1147-1160, 2007.
3. Galloway NR, Tong KA, Ashwal S, Oyoyo U, Obenaus A. Diffusion-weighted imaging improves outcome prediction in pediatric traumatic brain injury. J. Neurotrauma 25(10) 1153-1162, 2008.
4. Babikian T, Tong KA, Galloway NR, Freier-Randall MC, Obenaus A, Ashwal S. Diffusion-wieghted imaging predicts cognition in pediatric brain injury. Pediatr Neurol. 41(6) 406-412, 2009.
Sonia Hwang, M.B.A.
1st Year Ph.D. Student
Division of Biochemistry
Loma Linda University
Loma Linda, CA 92350
909-558-4000 (x81368)
shwang@llu.edu
Research Interests:
The purpose of my work was to continue work begun in the lab by Jon Aspe to determine if exosomes, collected from a melanoma cell line, built to harbor a tetracycline-regulated Survivin-T34A, contained the dominant negative and whether these exosomes could then affect pancreatic cancer cells in culture. I am currently producing and purifying exosomes that contain either the wildtype of dominant negative apoptosis-inducing survivin T34A and testing their survival/killing affects in combination with Gemcitabine.
Jessica Slater-Jutzy
4th Year Ph.D. Student
2nd Year Medical Student
Division of Biochemistry
Loma Linda University
Loma Linda, CA 92350
909-558-4000 (x81368)
jjutzy@llu.edu
Research Interests:
Cancer is one of the leading causes of death in the United States. The inability of the human immune system to eradicate malignant cells enhances the progression of tumor growth and disease. We believe tumor-released Survivin is a potential cause of this immune distortion and could provide an important target for therapy. My work has recently shown that Survivin in the tumor microenvironment has the capability to drive the tumor-mediated T lymphocyte skewing seen in cancer patients.
Selected peer-reviewed publications:
1. Khan S, Jutzy JMS, Aspe JR, Valenzuela MMA, Park J, Turay D, Wall NR. The Application of Membrane Vesicles for Cancer Therapy. Cancer Treatment/Book 3, 2011, ISBN 979-953-307-209-7.
2. Jutzy, JMS, Khan S, Valenzuela MMA, Milford TM, Payne KJ, Wall NR. Tumor-released survivin inhibits T cell proliferation and alters CD4+ T cell cytokine profiles to induce a pro-tumor environment. Cancer Microenvironment, 2012
3. Khan S, Jutzy JMS, Valenzuela MMA, Turay D, Aspe JR, Ashok A, Mirshahidi S, Mercola D, Lilly MB, Wall NR. Plasma-Derived Exosomal Survivin, a Plausible Biomarker for Early Detection of Prostate Cancer. PLoS One, 2012. In Press.
David Turay, M.D.
Assistant Professor, Surgery
5th Year Ph.D. Student
Division of Anatomy
Loma Linda University
Loma Linda, CA 92350
909-558-4000 (x81368)
dturay@llu.edu
Research Interests:
The work I am doing in the laboratory of Dr. Nathan Wall is to proteomically profile serum-derived exosomes from patients with prostate cancer. We believe that by studying the proteome of prostate-derived small membrane bound vesicles called exosomes, that perhaps an earlier and more specific biomarker may be found and that by understanding the relationship/interaction between proteins and RNAs and miRNAs within them, we may better understand the mechanisms of disease aggressiveness and treatment-resistance.
1. Khan S, Jutzy JMS, Aspe JR, Valenzuela MMA, Park J, Turay D, Wall NR. The Application of Membrane Vesicles for Cancer Therapy. Book 3, Advances in Cancer Therapy, InTech Publishing 2011, ISBN 978-953-307-703-1.
2. Khan S, Jutzy JMS, Valenzuela MMA, Turay D, Aspe JR, Ashok A, Mirshahidi S, Mercola D, Lilly MB, Wall NR. Plasma-Derived Exosomal Survivin, a Plausible Biomarker for Early Detection of Prostate Cancer. PLoS One, 2012. In Press.