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Salma Khan, PhD
Asst Res Prof, Basic Sciences
School of Medicine
Asst Res Prof, Medicine
School of Medicine
Asst Res Prof, Otolaryngology & Hed/Neck Surg
School of Medicine

I began my professional career as a Gynecologist in Bangladesh where woman prefers to consult with lady doctors only.  I have seen patients dying of cancers without treatment or lack of early diagnosis.  My journey began at that time to develop myself as a scientist who can explore the unsolved questions to cure cancer or to establish early diagnostic tools.  I then took the opportunity of Gov. of Japan’s scholarship for PhD degree in Gynecologic Pathology/Reproductive Physiology.  I have enjoyed every day of my life doing experiments and amazingly saw the research progress when Gleevac was marketed to save the life of Leukemia patients.  That’s the day, I decided to stay in cancer research field and discover some drugs to cure cancer or adjuvants to existing cancer therapy and encourage and educate my students to do so. â?¨â?¨

 

When I joined Loma Linda University, I have mastered myself in protein purification from a large scale culture Bio-reactor, Mass-spectrometric analysis, Flow-Cytometry (both cell cycle analysis by PI staining and cell-surface staining), exosome purification, confocal microscopy, siRNA, and Real-Time PCR.

 

While I was a post-doc researcher at Cedars-Sinai Medical Center since 2001 in a complex Pathology laboratory and research collaborative environment; providing molecular pathology support for a variety of projects in breast cancer, optimization and establishment of fluorescent in-situ hybridization (FISH) technique including synthesis of probe from BAC clone, labeling, and hybridizing into both metaphase spread and archival tissues, DNA purification from microdissected archival samples, Methylation specific PCR (MSP) to study epigenetic silencing of PTEN gene, primer optimization for LOH study primarily in breast, ovary, prostate cancer, and malignant melanoma.  My previous paper is on epigenetic titled ``PTEN promoter is methylated in a proportion of invasive breast cancers``, at International Journal of Cancer, 2005. â?¨â?¨

 

I am dedicated to establish myself as a Cancer Biologist.  As a Research Assistant Professor here in Loma Linda University, I have been successfully supervising MD/PhD students, Clinical fellows, and technicians in the research field.  As I emerged into a more national and international awareness of research informatics, I was particularly attracted to cancer biology.  It has thus far been an intense training in cancer biology field.  This training has endorsed my aspirations to keep me in more of a therapeutic approach.  Thus far, it has been re-tooling my scientific knowledge with the idioms, paradigms, and techniques of knowledge engineering and artificial knowledge in medicine.  This has led me to teach Cancer Biology course every spring series 2009 onwards to the graduate student at Loma Linda University and I have enjoyed teaching with enthusiasm with sound knowledge in cancer biology field. 

 

I have also prior experience in teaching and supervising the undergraduate students at Gandhi Medical College, Bhopal, India, as well as Cedars-Sinai Medical Center, at Los Angeles.  I have been teaching privileged to teach graduate students Cellular Mechanisms and Integrated system II (IBGS522) and IBGS 512, Winter Quarter, 2013.  I feel more comfortable and confident after I have gained my vast knowledge in extensive molecular biology and proteomics training. 

 

I have also published my work at British Journal of Cancer 2009 titled: Extracellular, cell-permeable surviving inhibits apoptosis while promoting proliferative and metastatic potential`` here at Loma Linda University.  I have come to a point where I want to find myself to invent a better cancer treatment strategies and pathway.  I have also established the exosome isolation methodologies in the lab. This work of mine was published atApoptosis 2011, titled: Survivin is released from Cancer cells via exosome. â?¨â?¨I have also published a translational research paper in PLosOne 2012, titled: Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer. 

 

As a part of my career development I have been applying for the foundation Grant (Susan G-Komen for cure), Department of Defense (DOD), and national Institute of Health (NIH: RO3, K22) (submitted).  I have been collaborating with both scientists and clinicians around the nation.  I have been a reviewer of Journal of Obstetrics & Gynecology Research, also involved as a reviewer of Graduate School comprehensive exam, and in the review committee of Annual Basic Science seminar for the Graduate students and post-docs.  I am also involved in teaching grant writing courses to students and post-docs at the University. 

 

In the division of Biochemistry, I can carry out research in the area of Systems Biology and Biological Regulation. We can develop a system to characterize the structural, biochemical, and in vivo functional properties of individual biomolecules and pathways with the cutting-edge approaches of modern genomics, proteomics, and metabolomics. I can train undergraduate students with the collaborations of other Universities and combine both experimental and computational approaches to model biological systems and tests the predictions of the models. A large number of investigators are addressing questions related to gene regulation at both transcriptional and post-transcriptional levels, metabolic regulation and homeostasis, regulation of cell shape and motility, intracellular transport and compartmentation, phylogenomics, and molecular evolution. Using Mass Spectrometers (GC-MS & LC-MS) we can identify differential expression of proteins in the tumor microenvironment using patients’ serum samples.

 

My recent proposed study is to identify a highly sensitive and specific molecular biomarker in thyroid cancer that can be used to effectively distinguish benign nodules in a fine needle aspiration (FNA) sample. Specifically, our team will use one-step real-time PCR technique to detect a novel oncoprotein called Enigma for the first time in all types of thyroid cancers: well-differentiated to poorly differentiated tissues.  As a graduate student in Japan, I studied morphological and pathological analysis of early placental development.  I also studied pathological analysis of rare ovarian cancer and cervical cancer biology.  I expanded this training to in-depth molecular pathology and molecular biology techniques in breast cancer and ovarian pathology during my post-doctoral training at Cedars-Sinai Medical Center in Los Angeles.  As a post-doctoral fellow at Loma Linda University (LLU), I further developed stable cell lines using cervical cancer cells to study the mechanism and interactions of an inhibitor of apoptosis protein called Survivin.  I also developed proteomic marker analysis of Survivin and its splice variants in breast cancer serum-derived exosomes (Khan et al, BMC cancer 2014).  As a Junior faculty at LLU where I am transitioning to independent and developing the thyroid cancer research program at the division of Biochemistry & Center for Health Disparities & Molecular Medicine to study thyroid cancer oncogenesis.  Collaborations with LLU faculty and outside resulted in two LLU-IRB approved protocols for obtaining primary fresh human surgical specimens and archival pathological samples that I have used to generate preliminary data.  Through a collaboration with Dr. Carr, all cell lines derived from human normal, benign, and different types of thyroid cancer tissues, will be used to establish functional interactions of two oncoproteins proposed in this study.  Having clinical background as well as a facilitator of translational research for basic scientists and as a member of Cancer Center and Internal Medicine Department, I am greatly committed to research that can be quickly transitioned to clinical use.  I can combine both biological techniques with biochemical techniques available in the division of Biochemistry and prepare them to be the expert in the future graduate school application or job field.

 

  1. 1.      Yousef S, Simental AA, Khan S. Proteomic profiling of tumor exosomes. Exosomes in Cancer; Diagnostic, Pharmaceutical and Therapeutic Applications. Editors: Amiji MM & Ramesh R. Published 2018.
  2. 2.      Firek A, Perez M, Chintalapati S, Lei L, Munir I, Gonda A, Carr FE,  Simental A, Becerra B, De Leon M, Khan S. Pathological significance of a novel oncoprotein in thyroid carcinogenesis. Head & Neck DOI: 10.1002/hed.24913: 2017; 1-11.
  3. 3.      Khan S, Simpson J, Lynch JC, Turay D, Mirshahidi S, Sanchez TW, Casiano CA, Wall NR. Racial differences in the expression of inhibitors of apoptosis (IAP) proteins in extracellular vesicles (EV) from prostate cancer patients.  PlosOne 2017 Oct 5;12(10):e0183122. doi: 10.1371/journal.pone.0183122.
  4. 4.      Xu J, Simental AA, Munir I, De Leon M, Khan S. Vitmain D pathway in Endocrine-related cancer: a literature review. (in press) Clinics in Surgery, 2017.
  5. 5.      Walters EL, Khan S. Cross-Generational aspects of gender in Medicine. Building my Village: Editor: Andy Thorp (in press) 2018.
  6. 6.      Khan S, Bennit FHR, Wall NR. The emerging role of exosomes in Survivin secretion. Histol & Histopathol, 30:43-50, 2015.
  7. 7.      Khan S, Bennit FHR, Valenzuela MMA, Turay D, Diaz Osterman CJ, Moyron RB, Esebanmen GE, Ashok A, Wall NR.  Localization and up regulation of Survivin in cancer health disparities: a clinical perspective. Biol: Targ Therap, 9:1-11, 2015.
  8. 8.      Turay D, Khan S, Osterman CD, Curtis MP, Khaira B, Neidigh JW, Mirshahidi S, Casiano CA, Wall NR. Proteomic profiling of serum-derived exosomes from ethnically diverse prostate cancer patients. Cancer Investigation, DOI: 10_3109/07357907.2015.1081921.
  9. 9.      Khan S, Bennit FHR, Perez M, Yuan Y, Mirshahidi S, and Wall NR.  Early diagnostic value of Survivin and its alternative splice variants in breast cancer. BMC Cancer doi: 10.1186/1471-2407-14-176, 2014.

10. Khan S, Yuan Y, Valenzuela MMA, Turay D, Ferguson H, Wong SF, Perez M, Mirshahidi S, Wall NR. Early diagnostic value of survivin and its alternative splice variants in breast cancers. J Clin Oncol 30:35, 2012.

11. Khan S, Jutzy JMS, Valenzuela MM, Turay D, Aspe JR, Ashok A, Lilly MB, Wall NR. Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer. PLOS ONE 7: e46737. doi: 10.1371, 2012.

12. Khan S, Jutzy JMS, Aspe JR, Valenzuela MM, Park J, Turay D, Wall NR. Application of Membrane Vesicles for Cancer Therapy. Advances in Cancer Therapy ISBN 979-953-307-209-7, 2011.

13. Khan S, Jutzy JMS, Aspe JR, McGregor DW, Neidigh JW, Wall NR. Survivin is released from cancer cells via exosomes.  Apoptosis 16: 1-12, 2011.

14. Pisarska MD, Bentsi-Barnes I, Barlow G, Khan S, Kuo F. LATS1 phosphorylates Forkhead L2 and regulates its activity as a transcriptional repressor of the Steroidogenic Acute Regulatory Gene.  Am J Physiol Endocrinol Metab 299: 101-109, 2010.

15. Khan S, Aspe JR, Asumen MG, Almguel F, Odumosu O, Acevedo-Martinez C, De Leon M, Wall NR. Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential.  Br J Cancer 100:1073-1086, 2009.

16. Khan S, Kumagai T, Vora J, Bose N, Sehgal I, Koeffler PH, Bose S.  PTEN promoter is methylated in a proportion of invasive breast cancers.  Int J Cancer 112: 407-410, 2004. Khan S, Katabuchi H, Araki M, Nishimura R, Okamura H. Human Villous Macrophage-Conditioned Media Enhance Human Trophoblasts Growth and Differentiation In Vitro.  Biol Repro 62: 1075-1083, 2000.

17. Khan S, Katabuchi H, Araki M, Ohba T, Koizumi T, Okamura H, Nishimura R.  The Molar Vesicle Fluid Contains the beta-Core Fragment of Human Chorionic Gonadotropin.  Placenta 21: 79-87, 2000.

18. Khan S, Katabuchi H, Okamura Y, Matsumura S, Nagai R, Ohtake H, Suenaga Y, Fukumatsu Y, Ikuta Y, Okamura H.  Malignant Soft Tissue Tumors of Ovary in Three Cases: Histology, Immunohistochemistry, and Ultrastructural Observation. Medical Electron Microscopy 31: 207-215, 1998.

19. Ohtake H, Katabuchi H, Tashiro H, Khan S, Fukumatsu Y, Okamura H.  Establishment of a New Cell Line, OKT1, from Small Cell Carcinoma Secreting Ectopic ACTH of the Uterine Cervix.  Gynecol Oncol 71: 177-184, 1998.

 

In Press:

  1. Xu J, Simental AA, Munir I, De Leon M, Khan S. Vitmain D pathway in Endocrine-related cancer: a literature review. (in press) J Surgical Oncology, 2017.
  2. Book chapter: Book Chapter: Walters EL, Khan S. Cross-Generational aspects of gender in Medicine. Building my Village: Editor: Andy Thorp (in press) 2018

Grants:

Extramural:

 

P20MD001632         De Leon (PI)                                               07/01/2012-06/30/2017

Sponsor: NIH/NIGMS                                         

Project title: Loma Linda University Center for Health Disparities Research

Goal: To use innovative approaches to eliminate cancer health disparities

Role: Key person as new investigator to establish a pilot project

 

Intramural

Current Research grants:

 

Division of Head & Neck Research fund        Khan (PI)          01/01/2017-01/01/2022               

Sponsor:  Otolaryngology, Loma Linda University School of Medicine:

$30,000/year for 5 years ($150,000)

Project Title: A novel oncoprotein differentially regulates progression from well differentiated to poorly differentiated aggressive phenotype

Goal: Identify a highly sensitive and specific biomarker for mutation negative thyroid cancers.

Role: PI

 

Riverside University Health System (RUHS) private fund:  Khan (PI) $12,000/yr, 2018-2020

Project title: Thyroid Carcinogenesis and pathway analysis.

Goal: Identify a novel pathway in thyroid cancer oncogenesis and treatment for anaplastic thyroid cancer.

Role: PI

 

Research Objectives:

 

Goal #1: Thyroid cancer health, gender, and racial disparities. With the support from Drs. DeLeon and collaborations of Drs. Alfred A. Simental, Chair of Head & Neck Surgery, Mia Perez (Pathologist, LLUMC), Iqbal Munir (Endocrinologist, Riverside University Medical Center), and Anthony Firek (Endocrinologist, Riverside University Medical Center), I am generating preliminary data on interplay between obesity-linked leptin and vitamin D binding protein (VDBP) polymorphism in thyroid cancer (TC) in Filipino Americans. VDBP is one of the key factors in Vitamin D trafficking into cells, contribute to low vitD available for thyroid tissues that led us to hypothesize that low vitamin D is one of the key upstream factors in thyroid carcinogenesis in Filipino populations. Preliminary data with 82% frequency rates of VDBP polymorphism in Filipino patients, we will confirm our findings by direct sequencing of VDBP by Dr. Charles Wang at Center for Genomic Research, while collecting at least 400 samples. We will also determine miRNA array by using next-gen sequencing. We are also planning to determine epigenetic modifications in both ethnicities. We also determine obesity-induced factors that can impact TC oncogenesis in the same genetic background.

Expression analysis of VDBP and correlation of the polymorphism with serum vitamin D/leptin levels in TC will be done. An orthotopic patient-derived Xenograft (OPDX) mouse model will be developed to get some more data on the functional study of leptin-vitamin D axis for my resubmission of NCI/HD/R01 grant.

 

miRNA let-7 expression in both ethnicities:

Filipino Americans are known to have higher rates of thyroid cancer incidence and disease recurrence than European Americans. They are also known to be 2 times more likely to die of thyroid cancer. Thyroid cancer has been linked to multiple factors, one of them being acculturation stress-induced obesity. Studies have shown that Filipino immigrants have a higher obesity rate than Filipinos who were born in the US; which leads us to the hypothesis that acculturation stress-induced obesity increases microRNAs (miRNAs) that lead to the thyroid cancer health disparities. Acculturation stress increases obesity that can increase exogenous stress that leads to endogenous stress and induces microRNA expressions, which contributes to cancer development. When deregulated, miRNAs can function as tumor suppressant genes or as oncogenes. One of the miRNA families of let is let-7, which is a family of 13 genes that are located on 9 different chromosomes and are one of the most expressed miRNAs in normal thyroid glands. Therefore, the let-7 family carries an important role in thyroid development and functionality. In this study, we expect to see the expression of let-7 and use this gene as a diagnostic, prognostic and predictive biomarker in thyroid cancer. In order to study this, we used QIAGEN’s DNA and miRNA extraction kits. Results from these extractions showed high quality and quantity DNA and miRNA obtained from paraffin-embedded thyroid tissues. We then proceeded to do miRNA qPCR assays to profile the let-7 miRNA expression. We found lower let-7 expression in Filipino American versus European American thyroid cancer tissues. In the future, we will do a miRNA-array analysis to distinguish miRNA profiles in Filipino Americans versus European Americans thyroid cancer tissues.

 

Goal #2: DIFFERENTIAL EXPRESSIONS OF C-SRC AND α-6 INTEGRIN IN WELL DIFFERENTIATED TO POORLY DIFFERENTIATED THYROID CANCER.

 

Thyroid cancer is categorized into different entities: well-differentiated thyroid cancer (WDTC), poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC). WDTC includes follicular and papillary thyroid cancer, whose characteristics are clearly noted with good prognosis. PDTC has a worse prognosis because the cancer cells grow faster than WDTC cells. PDTC also show to a higher risk of recurrence. ATC presents the worst prognosis. Patients usually die within 6 months after diagnosis. This creates a critical need to find out genes that are linked to PDTC/ATC progression and use them as therapeutic targets in the future. One of the targets is c-SRC, because it is expressed in many cancer types, including thyroid cancer. c-SRC is a cytoplasmic non-receptor protein kinase-encoding gene responsible for cell proliferation, survival, motility, migration, cytoskeleton regulation, and oncogenesis by mediating downstream signaling pathways. A higher expression of SRC in thyroid cancer cells are associated with thyroid cancer aggressive phenotypes. SRC is activated by a series of signaling proteins like integrins. Integrins are proteins that join the cytoskeleton of a cell to the extracellular matrix. Alpha-6, an integrin designed for epithelial tissue, uses the SRC signaling pathway to stimulate invasion. The purpose of our experiment was to examine whether SRC/alpha-6 are differentially expressed in WDTC and PDTC/ATC by immunohistochemistry. We determined the expression of SRC and Alpha-6 in deidentified thyroid cancer tissue specimens.  Tissue was processed through a series of deparaffinization, rehydration, antigen retrieval, antibody staining, and hematoxylin counterstaining steps. Our results show a higher expression of c-SRC in all subtypes of thyroid cancers than normal or benign tissues. The strongest expression was observed with a6 integrin in PDTC and ATC compared to WDTC. This data showed that c-SRC expression along with a6 integrin may be used as prognostic markers for aggressive phenotypes of thyroid cancer and targeted as future therapeutic strategies.

 

Research Skills:

 

Physiology/Biochemistry/molecular biology

  • Analysis of animal behavior
  • Analysis of physiology of ovarian maturation
  • Analysis of physiology of pregnancy
  • Analysis of placental development & maturation
  • Analysis of physiology of lactation
  • Physiology of thyroid hormone secretion and metabolism
  • Pathophysiology of diseases: Cardiovascular, renal, central nervous system, endocrine organs.
  • Human genetics, Molecular Pathology, Molecular Biology, Cancer Biology
  • Epigenetics, Tumor microenvironment, Apoptosis and Inhibition of Apoptosis
  • DNA Damage and Repair, Signal Transduction, Proteomics.

 

Expertise: Microscopy: Light, Fluorescent, Confocal Microscopy,

Archival Tissue: Tissue Array prep, Paraffin Section, Frozen section, Laser

Capture Microdissection, In-Situ Hybridization (ISH), Immunohisto-cytochemistry

(IHC), Fluorescent In-Situ Hybridization (FISH), In-Situ PCR, Triple

Immunoflurescent staining.

 

Molecular Cloning: Retro-Lentiviral Gene cloning, siRNA, miRNA, Plastic Membrane

Gene Chip Microarray analysis, Methylation-Specific PCR (MSP),

In-Cell Western Blot, Western Blot, Northern Blot, Real-Time PCR, Promoter

Analysis, Los of Heterozygosity (LOH) study, Single-nucleotide Polymorphism

(SNP), Cell Culture (Primary and Cell lines), Stable Cell line, Flow Cytometry

(Cell Cycle Analysis) Animal Model handling and Surgery.

 

Proteomics: Tap-tag Protein-purification, Exosome isolation and purification,

Mass-Spectrometric Analysis, ELISA, Apoptosis Assay, Immunoprecipitation,

Protein-Protein interaction (EMSA, Immunoprecipitation, Chromatin

Immunoprecipitation CHIP analysis)