Nominee: Omnia A Ismaiel, Zagazig University, Egypt
Nominated By: Rand Jenkins, PPD, USA
Supporting Comments: Omnia Ismaiel began working with PPD in 2008 as a postdoctoral fellow and became a full-time research scientist in early 2011. She has extensively studied matrix effects in LC–ESI-MS/MS bioanalysis, evaluating a broad spectrum of matrix lipid compound classes and their relative ion suppression interference effects. Over the past 2 years, Omnia’s research has focused on solid-phase microextraction and 2D UPLC separation techniques for analyzing peptides by LC–MS/MS. As part of this work, she assisted engineers from Waters Corporation in designing and testing a prototype Acquity UPLC® instrument with 2D technology that is now on the market. More recently, Omnia has contributed major work to our program on developing advanced LC–MS/MS assays for multiple β-amyloid biomarker peptides in CSF, intended to aid in the diagnosis and development of drugs to treat Alzheimer’s disease. This work is now reaching a major milestone of formal method validations for three assays, one of which involves close collaboration with the international Global Biomarker Standardization Consortium of the Alzheimer’s Association. This work has been very challenging, but also exciting and rewarding for Omnia. She is a highly productive research scientist and very deserving of recognition as a prominent young bioanalytical investigator and nominee of the Bioanalysis Young Investigator Award.
Bioanalysis Zone asked Omnia to highlight one of her favorite published articles and explain her reasoning.
Jenkins R, Ismaiel OA, Lin S, Shao J, Yuan M. A multiplex UPLC–MS/MS-based assay for amyloid β and related biomarker peptides in human cerebrospinal fluid. Alzheimer’s Dementia 7(4), S320 (2011).
What were the most difficult challenges encountered in this study? And how were they overcome?
A multiplex SPE–UPLC–MS/MS method has been developed that provides sensitive targeted detection of multiple amyloid β peptides (Aß) and related peptides in CSF in a single assay, which is extremely challenging owing to great hydrophobicity differences and tendency for nonspecific binding and self-aggregation. Protein low-binding containers were used to avoid nonspecific binding, DMSO has been used for preparation of stock solutions and working solutions to start with unaggregated monomeric peptides. High pH was carefully optimized during sample preparation to minimize self-aggregation. The analytes are separated under high pH, NH4OH-based, reversed-phase chromatographic conditions, intended to minimize nonspecific binding and aggregation. Because the analytes significantly vary in hydrophobicity, dramatically increasing over the range from Aβ1-14 to Aβ1-42, online aqueous dilution of the large sample extract band is required to ensure that the analyte peaks are efficiently focused on the precolumn. Following a brief desalting period with the precolumn effluent directed to waste, the valve is switched and the analytes are transferred to the analytical column and separated using an appropriate gradient.
What made you decide to study this particular field of bioanalysis? What makes it so appealing?
Alzheimer’s disease (AD) is the most common cause of dementia among older populations. Most proposed AD models postulate that abnormal accumulation of Aβ, fragments of the transmembrane amyloid precursor protein (APP), is closely associated with the disease process. Aß peptides analysis in CSF has found utility in clinical diagnosis. Aß1-42 CSF levels are known to decrease in AD patients. However, the population of Aß isoforms is complex, produced either through normal or abnormal secretase enzyme activities, there is on-going interest in having a ‘general-purpose’ assay that can simultaneously quantify a variety of selected target peptides to obtain a broader biomarker picture. While the longer length Aβ isoforms may be biomarkers of disease-related changes, the shorter C-terminal truncated isoforms, Aβ1-14 and Aβ1-15, are of interest as potential indicators of alternative degradation pathways for CNS APP during treatments with γ-secretase modulators or inhibitors. The relative level of APL1β28 (nonamyloidogenic Aβ-like peptide) also has been proposed as a more sensitive surrogate biomarker for Aβ1-42 production in the brain, as it may rise in parallel to Aβ1-42 from secretase-mediated overproduction without subsequently falling as may be occurring with Aβ1-42 due to plaque formation in AD brains.
Here is what some of Omnia’s friends and colleagues had to say about her.
H. Thomas Karnes, Virginia Commonwealth University, USA
“Omnia is an independent self-starter and has great potential for excellent success in the future. She consistently comes up with her own unique ideas on how to solve complex analytical problems. She has come a long way in her scientific development in such a short period of time, and has a large capacity for work. She handles stress very well and is a very positive person who never complains. I miss our scientific interaction very much but alas it is necessary to move on.”
Anwar Hamama, Virginia State University, USA
“Omnia has investigated systems to address the huge problem of phospholipid ion suppression matrix effects in bioanalytical LC–MS/MS. She has shown for the first time that phospholipids need to be monitored in routine analysis and when analyzing samples from various sources. Her projects have involved new bioanalytical systems for quantitative determination of pharmaceuticals in biological systems that are critical for highly relevant pharmaceutical investigations. Omnia has addressed matrix effect challenges with small molecules and is now working in the area of large peptide analysis, which is consistent with the direction that pharmaceutical development is heading.”
Hanaa Saleh, Zagazig University, Egypt
“Omnia works in a US FDA-regulated environment, which speaks to the relevance of her work. In addition to the work she has conducted on tracking matrix effects with small molecules in biological matrices, she has used LC–MS/MS and multiple-charge-state quantification for analysis of large therapeutic peptides, which is also an approach to control matrix effects in these complicated assays. Omnia has worked with, and educated, other PhD and undergraduate students, and post doctoral fellows effectively. She has been awarded an AAPS travel award as well as several awards from Zagazig University for her international publications.”
Hesham Ezzat, Zagazig University, Egypt
“Omnia for the first time published a library for different endogenous matrix components such as cholesterols and acylglycerols, in addition to phospholipids that may contribute to matrix effects – she created a normalized concentration suppression factor to compare matrix ionization effects resulting from these components. She teaches undergraduate pharmacy students and, in addition to her extraordinary scientific, teaching and research skills, she also gained outstanding experience in the pharmaceutical industry; she has explored real bioanalytical problems that may not arise in academia.”
Mervat Hosny, Zagazig University, Egypt
“Omnia has published many papers in peer-reviewed journals, her research either during her PhD studying or during her post-doctoral training was focused on very interesting and novel research. She was one of the first researchers that used endogenous phospholipids as a tool for assessment of matrix effects during samples analysis. Her original publications in this field have been cited by many researchers, and has also presented her work in many national and international conferences and meetings. She serves as a reviewer of manuscripts for many journals, and very much likes reading, playing music and traveling.”
Rand Jenkins, PPD, USA
“Omnia is very bright and highly motivated to explore new ideas and make advancements in her chosen field. She thoughtfully designs experiments and meticulously executes her research work with exceptional dedication and tenacity. Omnia has a depth of experience and level of scientific maturity that is unusual for someone her age. She received excellent training as a bioanalyst in her PhD program under Professor Karnes and subsequently participated in many challenging projects within our research and development group at PPD. Outside the laboratory, Omnia enjoys playing music, taking photographs and traveling. I believe she will have a very successful future as a bioanalyst in either industry or academia.”