Dr. Houda Alachkar received her Ph.D. in Biomedical Sciences from the Ohio State University under the mentorship of Prof. Guido Marcucci and received her PharmD degree from Ohio Northern University. Dr. Alachkar received postdoctoral fellowship training in clinical pharmacology and pharmacogenomcis with Prof. Yusuke Nakamura and Prof. Wendy Stock at the University of Chicago. In September 2015, she joined the University of Southern California (USC) School of Pharmacy as an Assistant Professor. The Alachkar lab focuses on applying genomic information to the identification and functional characterization of cancer targets, and in the preclinical and clinical developments of potential targeted therapeutic approaches with particular interest in acute myeloid leukemia.
Areas of Expertise (5)
Acute Myeloid Leukemia
University of Chicago: Fellowship, Clinical Pharmacology and Pharmacogenomics
Ohio State University: Ph.D., Biomedical Sciences
Ohio Northern University: Pharm.D.
Selected Media Appearances (1)
USC School of Pharmacy Study Sheds New Light on Targeted Drugs to Treat Acute Myeloid Leukemia
USC School of Pharmacy online
Midostaurin reduces regulatory t cells markers, according to researchers in the Alachkar lab at the USC School of Pharmacy
Research Focus (1)
The Alachkar Lab
The revolution in sequencing technologies has given the momentum for the emerging genomics and personalized medicine era that led to great discoveries, particularly in cancer research. Translating these findings into the clinic, however, has moved at a much slower pace. It is evident that cancer pharmacogenomic variation, the somatic changes in cancer cells and germline variants in normal cells, influence the disease outcome and response to treatment.
The Alachkar lab focuses on applying genomic information to the identification and functional characterization of cancer targets, and in the preclinical and clinical developments of potential targeted therapeutic approaches with particular interest in acute myeloid leukemia.
Selected Articles (7)
Vijaya Pooja Vaikari, Yang Du, Sharon Wu, Tian Zhang, Klaus Metzeler, Aarif M.N. Batcha, Tobias Herold, Wolfgang Hiddemann, Mojtaba Akhtari, Houda Alachkar
In an effort to identify target genes in acute myeloid leukemia, we compared gene expression profiles between normal and acute myeloid leukemia cells from various publicly available datasets. We identified CD99, a gene that is upregulated in patients with acute myeloid leukemia. In 186 patients from The Cancer Genome Atlas - acute myeloid leukemia dataset, CD99 was overexpressed in patients with FLT3-ITD and was downregulated in patients with TP53 mutations.
Vijaya Pooja Vaikari, Jiawen Yang, Sharon Wu, Houda Alachkar
CD97, a member of the adhesion G-protein coupled receptor family, is normally expressed on leukocytes and smooth muscles. CD97 is also expressed in a variety of solid cancers, particularly those with aggressive metastatic phenotypes. Here we characterize the clinical significance of CD97 in acute myeloid leukemia (AML). We analyzed 173 patients from the TCGA AML data set and found that CD97 was higher in cytogenetically normal patients compared with cytogenetically abnormal patients (p = 0.023). High CD97 was also associated with NPM1 mutations (p = 0.0033). Patients with high CD97 expression had shorter overall (median: 7.35 months vs. 24.1 months, p = 0.0015) and disease-free (median DFS: 8.2 months vs. 18.2 months, p = 0.017) survival. Importantly, we identified pathways involved in the leukemia stem cell interaction with the bone marrow niche, such as integrin, CXCR4, and interleukin-8, among the most upregulated signaling pathways in patients with high CD97 expression. Our results suggest that high CD97 expression is associated with poor clinical outcome and indicate a need for future functional and mechanistic studies to investigate the role of CD97 in AML.
Sharon Wu, Nicole Fahmy, Houda Alachkar
Acute myeloid leukemia (AML) is characterized by rapid growth of abnormal blasts that overcrowd normal hematopoiesis. Defective mitochondrial biogenesis has been implicated in AML, which we believe is partly due to the deregulation of the mitochondrial transcription machinery (MTM) genes influencing the expression of mitochondrial genes. Here, we aim to characterize MTM gene upregulation in AML.
Jiawen Yang, Sharon Wu, Houda Alachkar
The role of adhesion G protein-coupled receptors (aGPCRs) in cancer has become increasingly evident in recent years. Yet, data supporting the contribution of this family of genes to hematological malignancies, particularly acute myeloid leukemia (AML) are limited. Here, we use publicly available genomic data to characterize the expression of the 33 aGPCRs in patients with AML and examine whether upregulation of these genes is associated with the clinical and molecular characteristics of patients. Upregulation in one or more of eight aGPCR genes (ADGRB1, ADGRC2, ADGRD1, ADGRE1, ADGRE2, ADGRE5, ADGRG1, and/or ADGRG3) was significantly associated with shorter overall survival (OS) (median OS: 11.8 vs 55.4 months; P < 0.0001). This was also significant in multivariate survival analysis (hazard ratio: 1.73; 95% confidence interval 1.11–2.69; P = 0.015) after adjusting for age, molecular risk status, and transplant status. High expression of the eight aGPCRs was significantly associated with older age (≥60; P = 0.011). Patients with high aGPCRs expression were more frequently classified in the poor molecular risk status group and less in the good risk status group compared with patients with low aGPCRs expression (31% vs 17% P = 0.049 and 14% vs 28% P = 0.027, respectively). Via Ingenuity Pathway Analysis, we identified the interleukin-8 signaling pathway among the most activated pathways in patients with high aGPCRs expression. Overall, our data suggest that particular aGPCRs are frequently upregulated in AML and associated with poor clinical outcome. Future functional and mechanistic analyses are needed to address the role of aGPCRs in AML.
Sharon Wu, Mojtaba Akhtari & Houda Alachkar
Acute Myeloid Leukemia is a devastating and heterogeneous, hematological malignancy characterized by the uncontrolled proliferation of undifferentiated myeloid progenitor cells—blasts. Mutations in certain mitochondrial proteins, such as IDH2 have been shown to contribute to leukemogenesis.
Vassiliki Saloura, Hyun-Soo Cho, Kazuma Kiyotani, Houda Alachkar, Zhixiang Zuo, Makoto Nakakido, Tatsuhiko Tsunoda, Tanguy Seiwert, Mark Lingen, Jonathan Licht, Yusuke Nakamura, Ryuji Hamamoto
Squamous cell carcinoma of the head and neck (SCCHN) is a relatively common malignancy with suboptimal long-term prognosis, thus new treatment strategies are urgently needed. Over the last decade, histone methyltransferases (HMT) have been recognized as promising targets for cancer therapy, but their mechanism of action in most solid tumors, including SCCHN, remains to be elucidated. This study investigated the role of Wolf–Hirschhorn syndrome candidate 1 (WHSC1), an NSD family HMT, in SCCHN. Immunohistochemical analysis of locoregionally advanced SCCHN, dysplastic, and normal epithelial tissue specimens revealed that WHSC1 expression and dimethylation of histone H3 lysine 36 (H3K36me2) were significantly higher in SCCHN tissues than in normal epithelium. Both WHSC1 expression and H3K36me2 levels were significantly correlated with histologic grade. WHSC1 knockdown in multiple SCCHN cell lines resulted in significant growth suppression, induction of apoptosis, and delay of the cell-cycle progression. Immunoblot and immunocytochemical analyses in SCCHN cells demonstrated that WHSC1 induced H3K36me2 and H3K36me3. Microarray expression profile analysis revealed NIMA-related kinase-7 (NEK7) to be a downstream target gene of WHSC1, and chromatin immunoprecipitation (ChIP) assays showed that NEK7 was directly regulated by WHSC1 through H3K36me2. Furthermore, similar to WHSC1, NEK7 knockdown significantly reduced cell-cycle progression, indicating that NEK7 is a key player in the molecular pathway regulated by WHSC1.
Ryan M Smith, Houda Alachkar, Audrey C Papp, Danxin Wang, Deborah C Mash, Jen-Chyong Wang, Laura J Bierut, Wolfgang Sadee
CHRNA5, encoding the nicotinic α5 subunit, is implicated in multiple disorders, including nicotine addiction and lung cancer. Previous studies demonstrate significant associations between promoter polymorphisms and CHRNA5 mRNA expression, but the responsible sequence variants remain uncertain. To search for cis-regulatory variants, we measured allele-specific mRNA expression of CHRNA5 in human prefrontal cortex autopsy tissues and scanned the CHRNA5 locus for regulatory variants. A cluster of six frequent single-nucleotide polymorphisms (rs1979905, rs1979906, rs1979907, rs880395, rs905740, and rs7164030), in complete linkage disequilibrium (LD), fully account for a >2.5-fold allelic expression difference and a fourfold increase in overall CHRNA5 mRNA expression. This proposed enhancer region resides more than 13 kilobases upstream of the CHRNA5 transcription start site. The same upstream variants failed to affect CHRNA5 mRNA expression in peripheral blood lymphocytes, indicating tissue-specific gene regulation. Other promoter polymorphisms were also correlated with overall CHRNA5 mRNA expression in the brain, but were inconsistent with allelic mRNA expression ratios, a robust and proximate measure of cis-regulatory variants. The enhancer region and the nonsynonymous polymorphism rs16969968 generate three main haplotypes that alter the risk of developing nicotine dependence. Ethnic differences in LD across the CHRNA5 locus require consideration of upstream enhancer variants when testing clinical associations.