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  1. Science & Research (Biologics)

Novel and Emerging Therapies for Food Allergy

Alexander S. Zhovmer, PhD

Office of Vaccines Research and Review
Division of Bacterial, Parasitic, and Allergenic Products
Laboratory of Immunobiochemistry

Alexander.Zhovmer@fda.hhs.gov


Biosketch

Dr. Alexander S. Zhovmer serves as a Principal Investigator in the Laboratory of Immunobiochemistry, studying the immunology of food allergy. He received a master’s degree in medical biology at the Novosibirsk State University, working on the immunology of breast cancer at the Institute of Clinical Immunology in Novosibirsk, Russia. During his Ph.D. training at the University of Strasbourg, he worked with Drs. Frederic Coin and Jean-Marc Egly at the Institute of Genetics and Molecular and Cellular Biology in Illkirch-Graffenstaden, France, discovering novel mechanisms of DNA damage detection and repair. During his postdoctoral training with Dr. Xiaohui Qu at the Memorial Sloan Kettering Cancer Center in New York, he developed new methods for quantitative single-molecule analysis of eukaryotic gene expression. Working with Dr. Robert Adelstein at the National Heart, Lung, and Blood Institute, NIH, he combined human and mouse genetics, advanced imaging, and biomimetic engineering to uncover mechanisms regulating immune cell motility and shape established through interactions with the extracellular matrix.

Currently, Dr. Alexander Zhovmer studies prospective immunotherapies for food allergy, allergenic imprinting, and mechanisms of coordinated actions of immune cells in tissues.


Overview

After cancer, AIDS, and cardiovascular illnesses, allergies are the fourth most common global pathologic condition, affecting up to half of the population in the industrialized countries. More than half of all Americans are impacted by food allergies and sensitivities, including multi-food allergies. The latter are more prevalent among non-Hispanic Black and Asian children compared to non-Hispanic White children, as well as more prevalent among inner-city populations with asthma. Food allergies typically manifest via local inflammation in gastrointestinal tract, lungs, and skin, but sometimes allergic reactions progress to potentially lethal anaphylaxis. Along with venom and drug allergies, food allergies rank among the top three causes of anaphylaxis, and the severity and incidence of food allergies has steadily increased over the past two decades.

In the U.S., the prevalence of food allergies in children increased by 50% between 1997 and 2011, and for peanut and tree nut allergies the prevalence more than tripled between 1997 and 2008. Similarly, childhood hospitalizations for food allergy tripled between the late 1990s and the mid-2000s. Anaphylactic reactions resulting from food allergy increased by 377% between 2007 and 2016. The cost of living with food allergies has become a financial burden, both on affected individuals and on the public health system. Childhood food allergies alone cost the U.S. $24.8 billion annually, including $5.5 billion in out-of-pocket costs to families.

Current options for treatment of food allergies are limited. However, recent advances in preclinical and clinical immunotherapy studies have greatly broadened the potential to manipulate immune system in patients with allergies, counteracting pathological immune responses. These new approaches include allergen immunotherapy, DNA or viral-like particle vaccines, biologics such as anti-IgE antibodies, as well as gene and cell therapy with gene-modified immune cells. Since FDA oversees clinical studies designed to support the safety and effectiveness of these new investigational products, our research program focuses on studying novel and emerging therapies for food allergy. The research thereby develops expertise, collects data, and creates technologies which impact new products to protect and advance public health.

In our research program, we develop animal models of emerging therapies for food allergy. This work promotes accurate and comprehensive characterization of the safety, efficacy, quality, and performance of the products FDA regulates. Furthermore, to evaluate emerging therapies, we combine animal models with biomarker panels, advanced in vitro platforms, and state-of-the-art methods such as physiological-like elastic hydrogels and nanotextured 3D systems, AI-enhanced super-resolution microscopy, and multiplexed tissue imaging. Using these tools, we study: (a) the physiological and pathological behavior of immune cells in tissues, (b) therapeutic effects and potential adverse reactions to prototype products, and (c) the potential for establishment of permanent immunologic tolerance to common foods by using gene and cell therapy approaches.


Important Links


Publications

  1. Sci Adv 2024 Jan 5;10(1):eadi1788
    Septins provide microenvironment sensing and cortical actomyosin partitioning in motile amoeboid T lymphocytes.
    Zhovmer AS, Manning A, Smith C, Nguyen A, Prince O, Sáez PJ, Ma X, Tsygankov D, Cartagena-Rivera AX, Singh NA, Singh RK, Tabdanov ED
  2. Adv Sci 2023 Nov;10(31):e2302229
    Dynein-powered cell locomotion guides metastasis of breast cancer.
    Tagay Y, Kheirabadi S, Ataie Z, Singh RK, Prince O, Nguyen A, Zhovmer AS, Ma X, Sheikhi A, Tsygankov D, Tabdanov ED
  3. Cancers 2023 Jun 30;15(13):3432
    Vitamin D receptor antagonist MeTC7 inhibits PD-L1.
    Khazan N, Quarato ER, Singh NA, Snyder CWA, Moore T, Miller JP, Yasui M, Teramoto Y, Goto T, Reshi S, Hong J, Zhang N, Pandey D, Srivastava P, Morell A, Kawano H, Kawano Y, Conley T, Sahasrabudhe DM, Yano N, Miyamoto H, Aljitawi O, Liesveld J, Becker MW, Calvi LM, Zhovmer AS, Tabdanov ED, Dokholyan NV, Linehan DC, Hansen JN, Gerber SA, Sharon A, Khera MK, Jurutka PW, Rochel N, Kim KK, Rowswell-Turner RB, Singh RK, Moore RG
  4. ACS Nano 2021 Nov 23;15(11):17528-48
    Mechanical counterbalance of kinesin and dynein motors in a microtubular network regulates cell mechanics, 3D architecture, and mechanosensing.
    Zhovmer AS, Manning A, Smith C, Hayes JB, Burnette DT, Wang J, Cartagena-Rivera AX, Dokholyan NV, Singh RK, Tabdanov ED
  5. Nanomedicine 2021 Oct;37:102442
    Programmable DNA-augmented hydrogels for controlled activation of human lymphocytes.
    Zhovmer AS, Chandler M, Manning A, Afonin KA, Tabdanov E
  6. Nat Commun 2021 May 14;12(1):2815
    Engineering T cells to enhance 3D migration through structurally and mechanically complex tumor microenvironments.
    Tabdanov ED, Rodríguez-Merced NJ, Cartagena-Rivera AX, Puram VV, Callaway MK, Ensminger EA, Pomeroy EJ, Yamamoto K, Lahr WS, Webber BR, Moriarity BS, Zhovmer AS, Provenzano PP

 

 
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